After a $2.5 billion financing round, MNC reinvests $25 million in Suzhou-based pharmaceutical company Adagene

On July 1, Sanofi plans to make a strategic investment of up to $25 million in Adagene. The funds will primarily be used to advance product development, with key support forAnti-CTLA-4 SAFEbody® safety antibody Muzastotug (ADG126) in microsatellite stable colorectal cancer (MSS CRC)Phase 2 clinical trial。

At the same time, Adagene will supply the drug to Sanofi for use in a clinical trial targeting patients with advanced solid tumors.Phase 1/2 combination therapy clinical trial, to evaluate the safety, efficacy, pharmacokinetics, and biomarkers of the combination therapy, with over 100 patients expected to be enrolled.Adagene retains global commercialization rights for Muzastotug.

In addition, Sanofi will initiate the third antibody development program under the joint SAFEbody® collaboration framework, andPay option fees, development milestone payments, and tiered royalties based on sales.This project will develop a undisclosed-target bispecific antibody based on Adagene's proprietary SAFEbody® technology and antibody engineering platform.

This strategic investment and antibody option exercise trace back to the 2022 collaboration—both parties initiated a multi-target partnership on Adagene's proprietary SAFEbody® technology to develop next-generation masked antibody candidates, with potential total transaction value reaching $2.5 billion plus royalties. Sanofi paid Adagene an upfront payment of $17.5 million.First launch two Sanofi antibody candidate drugsengage in cooperative development, andEntitled to nominate two additional candidate antibody drugsCarry out development and commercialization.

In fact, this strategic investment can be regarded as a further deepening of the collaboration between Sanofi and Adagene:Not only advanced Adagene's Phase 2 clinical trial and the joint combination therapy Phase 1/2 clinical trial with Sanofi, but also exercised the additional provisions in the 2022 agreement—initiating a third antibody development program.

As of December 31, 2024, Adagene's audited cash and cash equivalents amounted to $85.2 million. Combined with Sanofi's current investment, the funds are expected to support operations through 2027. According to the equity investment and strategic cooperation agreement,Sanofi will appoint a representative to join Adagene's Scientific Advisory Board (SAB) to provide strategic advice on its research and development efforts.

As a platform-driven company, Adagene is dedicated to discovering and developing novel cancer immunotherapies based on original antibodies. Leveraging computational biology and artificial intelligence, the company owns the world's first trinity platform technologies: the Neotope Antibody (NEObody™), the SAFEbody® platform, and the POWERbody™ platform. The collaboration with Sanofi primarily focuses on its unique SAFEbody® platform.

Safe antibodySAFEbody® technology maximizesMitigate toxic side effects caused by targeting antigens expressed in healthy tissues, addressing the safety and tolerability issues of antibody therapiesBy specifically activating within the tumor microenvironment, safe antibodies can achieve precise targeting and tumor suppression in tumor tissues, while minimizing toxic side effects on surrounding healthy tissues.

Muzastotug (ADG126) is Adagene's first clinical-stage SAFEbody® program, which is aA masked anti-CTLA-4 therapy. Muzastotug viaSafe antibodySAFEbody® precision masking technology is applied to the parent antibody ADG116 to enable specific activation within the tumor microenvironment, thereby improving the therapeutic index by addressing the dose-dependent toxicity issues associated with effective dosing and optimized dosing regimens of existing anti-CTLA-4 therapies.

Moreover,Muzastotug binds to the same highly conserved unique epitope as ADG116, effectively depleting regulatory T cells (Treg) within the tumor microenvironment and exerting partial ligand blockade, thereby steadily accumulating and prolonging the drug's tumor-killing effect, enhancing both safety and efficacy.

CTLA-4（CytotoxicityT lymphocyte-related protein 4), isA transmembrane receptor on T cells that acts as an immune checkpoint "switch" to downregulate immune responses. Anti-CTLA-4 therapyby inhibitingCTLA-4 molecule, causing massive proliferation of T cells and attack on tumor cells. Anti-CTLA-4 is known for its dose-dependent clinical responses in monotherapy and combination therapies, butExisting antiHowever, CTLA-4 therapy has faced challenges due to itsNarrow therapeutic windowSeverely limits clinical benefits.

The key point is that immune checkpoints such as anti-CTLA-4 serve only as one component of a multi-layered immune regulatory mechanism.RegulatoryThe activity of regulatory T cells (Treg) constitutes another layer of immune regulation.Safe antibodyAble to target simultaneouslyTumor microenvironmentChinaTregImmune modulation, thereby opening upantiCTLA-4 therapyTherapeutic window, overcoming dosage limitations.

GLP toxicology studies show that the maximum safe range of Muzastotug targeting CTLA-4 is as high as 200 mg/kg, significantly increasing the likelihood of optimal clinical dosing for patients in both monotherapy and combination therapy. Results from a dose optimization study indicate that Muzastotug (administered at 10 mg/kg every three weeks) in combination with anti-PD-1 therapy, compared to ipilimumab (administered at 1 mg/kg every six weeks) in combination with anti-PD-1 therapy,Its therapeutic index is increased by up to30x. Therefore, MuzastotugCan be administered at higher doses, higher frequencies, and repeatedly combined with antiPD-1 repeated administration. In addition, the data results show that this combination therapy can produceDose-dependent efficacy, and treatment-related adverse events (TRAE did not increase significantly.

In terms of the first indication, microsatellite stable colorectal cancer (MSS CRC) accounts for approximately 95% of patients with metastatic colorectal cancer. Microsatellite stable tumors are referred to as"Cold" tumor, as they typically do not provoke a strong immune response from the human body. Currently, there are no approved cancer immunotherapies for microsatellite stable colorectal cancer.

In the 1b/2 phase clinical data of Muzastotug in combination with pembrolizumab for MSS CRC released in 2025,The dosing regimen significantly reduced treatment-related toxicity, and no patient discontinued treatment due to adverse reactions.In a group of 67 MSS CRC patients without liver metastasis, the objective response rate (ORR) was 17% in the 10 mg/kg every three weeks group, whileThe confirmed ORR in the 20 mg/kg group was 29%.The median duration of response (DoR) in the 10 mg/kg group was 6.2 months, while the median DoR in the 20 mg/kg group has not yet been reached, and all responding cases are still undergoing treatment.

10 mg/kg groupThe median overall survival (OS) was 19.4 months., demonstrating superior performance compared to current standard therapies and historical control data; the Kaplan-Meier overall survival curve for the 20 mg/kg group has初步 shown early separation from the historical control group, suggestingPotential long-term survival benefit。

Investing in Adagene is Sanofi's continued bet on next-generation oncology drugs.

As early as 2019, Sanofi announced it would discontinue the development of new diabetes and cardiovascular drugs, shifting focus to more profitable areas such as oncology, and has since strengthened its oncology drug pipeline starting from 2020, including multiple anti-cancer bispecific and trispecific antibodies developed with its long-term partner Regeneron.

In January 2020, Sanofi acquired Synthorx for a total transaction value of approximately $2.5 billion, or $68 per share (a premium of about 172%), gaining an IL-2-targeted therapy, Thor-707.

In March 2020, Sanofi's anti-CD38 monoclonal antibody isatuximab was approved for use in combination with pomalidomide and dexamethasone for the treatment of adult patients with relapsed and refractory multiple myeloma who have received at least two prior therapies, including pomalidomide and a proteasome inhibitor, becomingThe first FDA-approved oncology drug fully owned by Sanofi in ten years。

In January 2025, isatuximab was approved by the National Medical Products Administration (NMPA) for use in combination with pomalidomide and dexamethasone to treat adult patients with multiple myeloma who have received at least one prior line of therapy, including lenalidomide and a proteasome inhibitor.

In August 2022, Sanofi made a rare large investment—byInvested 600 million euros (approximately 4 billion RMB) in equity to acquire a stake in Innovent Biologics.The final agreement amount reached 740 million euros, approximately 5.1 billion Chinese yuan.Meanwhile, Innovent Biologics introduced two late-stage clinical oncology assets from Sanofi—CEACAM5 ADC and biased IL-2 (from Synthorx)—with zero upfront payment, and will lead their clinical development in China.

Although both collaborative pipelines have terminated development, butThe 20% premium for acquiring a stake in Innovent Biologics at its lowest point clearly reflects Sanofi's emphasis on the Chinese market and its confidence in Chinese innovative pharmaceutical companies.

“"Complementary oncology pipelines" might be the key reason why Sanofi has twice acquired shares in Chinese pharmaceutical companies.From a potential total amount of $2.5 billion BD, to a $25 million strategic investment, exercising the antibody selection right under clause 3 and milestone payments,The focus of the investment is on Adagene's SAFEbody® safety antibody technology platform.

In the 2022 cooperation framework between both parties,Global Head of Oncology R&D at SanofiValeria Fantin said, "For pathways that have been extensively explored but whose tumor mechanisms remain unclear, Adagene"Our unique antibody platform will enable us to precisely target well-established yet poorly addressed oncology mechanisms with best-in-class therapeutics."Data shows, safety antibody technology"Can be widely used for multiple antibody formats, including monoclonal and bispecific antibodies, such asFc receptor antibodies, antibody-drug conjugates, and T-cell engagers.