China’s ProfoundBio, a biotech company based in the Seattle area, WA, USA and Suzhou, China, focuses on the development of novel targeted therapies. Earlier this week the company confirmed that it has closed a US $ 70 million Series A+ financing round led by Sequoia China. Current investors, including Lilly Asia Venture, Oriza, Chang’an Capital, LYFE Capital, and K2VC also participated in this round of financing.
PRO1184 is an antibody-drug conjugate (ADC) directed toward folate receptor alpha (FOLR1), a glycosyl phosphatidylinositol anchored membrane protein. FOLR1 is overexpressed in many cancers with unmet medical need, including ovarian, lung, and breast cancers, while normal tissue expression is limited.
The investigational drug is comprised of a human monoclonal antibody that selectively binds to FOLR1, a cleavable, hydrophilic linker, and exatecan, a topoisomerase 1 inhibitor.
Mechanism of Action
Upon binding to FOLR1 on the surface of malignant cells, PRO1184 is internalized and exatecan released through enzymatic cleavage of the linker. Exatecan blocks the ligation step of the cell cycle and generates DNA single- and double-strand breaks, which leads to cell death.
In a number of different studies, the mechanism of action and clinical potential of PRO1184 was investigated. the results showed that PRO1184 bound selectively and specifically to FOLR1 with nM affinity and was efficiently internalized and demonstrated cytotoxicity against multiple cell lines, in vitro. In mouse carcinoma models, PRO1184 demonstrated robust anti-tumor activity across multiple tumor types that represent ovarian, non-small cell lung, and breast cancer.
Results from studies, presented during the annual meeting of the American Association for Cancer Research (AACR), held April 8-13, 2022 in Philadelphia, USA, also demonstrated that PRO1184 was more potent with greater tumor growth inhibition than that of a DM4-conjugated ADC.
PRO1184 was tolerated at the 60 mg/kg dose level in cynomolgus monkeys and the safety profile was generally more favorable than that for a DXd-based ADC. The pharmacokinetics (PK) of PRO1184 were similar to that of the unconjugated parent antibody in rats. PRO1184 has the potential for a meaningful therapeutic window to provide an appropriate benefit to risk profile for patients with FOLR1-expressing cancers.
PRO1160 is a CD70-directed ADC for both hematological and solid tumor indications. Preclinical studies suggest that both compounds may achieve favorable benefit to risk profiles in the clinic. CD70 is aberrantly overexpressed in multiple hematologic malignancies and carcinomas with limited normal tissue expression.
The investigational ADC is comprised of a human monoclonal antibody that selectively binds to CD70, a cleavable, hydrophilic linker, and exatecan, a topoisomerase 1 inhibitor payload. Upon binding to CD70 on the surface of malignant cells, PRO1160 is internalized and exatecan released through enzymatic cleavage of the linker. Exatecan blocks the ligation step of the cell cycle and generates DNA single- and double-strand breaks, which leads to cell death.
Data based on in vivo and in vitro studies with PRO1160, presented during the AACR annual meeting demonstrated robust anti-tumor activity. In addition, in multiple cell-derived xenograft mouse models, PRO1160 demonstrated more potent tumor growth inhibition compared to an MMAE-conjugated ADC with the same parent antibody.
PRO1160 was well tolerated in mice with no to minimal impact on body weight gain. The in vivo pharmacokinetics in rats showed that PRO1160 is stable in circulation. Based on these nonclinical data, researchers believe that there is a potential for a broad therapeutic window warranting and further development.
Accelerating earl-stage development programs
Additionally, the company will continue to accelerate multiple early-stage programs to preclinical and CMC development, strengthen and expand innovative ADC technologies, and establish vertically integrated development capabilities to streamline discovery to clinical trials.
“This financing, especially in the context of this challenging economic environment, represents the confidence our new and all our current investors have in our capabilities, pipeline, and ADC technology.” said Baiteng Zhao, Ph.D, co-founder, CEO, and Chair of the Board of ProfoundBio.
“We made tremendous advancements as we continue to execute on our plan to bring novel therapeutics to patients with cancer. We will soon submit an IND for PRO1184, already initiated IND-enabling activities for PRO1160, and continue to expand our pipeline. In addition, we established multiple novel ADC technology platforms as presented at the 2022 AACR annual meeting. Finally, and of equal importance, our team continues to strengthen with numerous key people identifying with and wanting to be a part of our vision,” Zhao added.
 Baiteng Zhao, Lei Wang, Haidong Liu, Suping Huang, Xiao Shang, Tae Han. PRO1184, a novel folate receptor alpha-directed antibody-drug conjugate, demonstrates robust anti-tumor activity in mouse carcinoma models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1085.
 Lei Wang, Haidong Liu, Xiao Shang, Tae Han, Baiteng Zhao. PRO1160, a novel CD70-directed antibody-drug conjugate, demonstrates robust anti-tumor activity in mouse models of renal cell carcinoma and non-Hodgkin lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1759
Featured Image: Attendees during the AACR 2016 Annual Meeting – April 19, 2016. Photo Courtesy: © AACR/Scott Morgan 2016. Used with permission.