ADC Review – Onco’Zine
Annual World ADC – Best New Drug Developer 2020: Sutro Biopharma’s Journey to Success
William J. Newell
Published Nov. 5, 2020
From liquid biopsies to precision medicine to immunology, the field of cancer treatment has experienced significant progress during the last decade. Although according to the American Cancer Society more than 80% of those diagnosed with cancer in the United States are 55-years-old or older, many are living longer, full lives despite their disease. Cancer detection and treatment have greatly improved since the first use of radiation therapy in 1899.[1]
At Sutro, we are pioneering a unique way of discovering, developing and manufacturing therapeutics for cancer with a focus on next-generation therapeutics, including antibody-drug conjugates (ADCs), bispecific antibodies and cytokine derivatives.
We have the world’s only cGMP cell-free manufacturing facility located in San Carlos, Calif., where we are unconstrained by the traditional limitations of cell-based discovery. Our technology enables us to iteratively discover and test molecules in a rapid cycle of weeks rather than months to identify the optimal molecule designed for safety and potency. Through this approach, we have the ability to design and develop targeted therapeutics by innovating outside the constraints of the cell. Sutro’s proprietary and integrated cell-free protein synthesis and site-specific conjugation platform, XpressCF+™, led to the discovery of STRO-001 and STRO-002 (Sutro’s first two internally-developed ADCs), as well as CC-99712 which is being developed clinically by Bristol Myers Squibb.
World ADC Digital Event
We have been working tirelessly to develop and bring much-needed therapies to patients, especially those that have exhausted all approved treatment options. This year we are honored to have been recognized as Best New Drug Developer at the World ADC Digital Awards, held during the World ADC Digital Event. This award recognizes our innovative clinical development candidate ADCs and represents a recognition by some of the most talented professionals in the biopharmaceutical industry. This award acknowledges the innovation, commitment and contributions of our talented team at Sutro.
The World ADC Awards showcase companies, teams and individuals in the industry, across 9 categories, at the forefront of cancer research today. Finalists and winners were shortlisted from over 1,000 votes cast and each submission was evaluated by a panel of seven judges. The awards ceremony virtually took place on September 17, 2020
Novel Antibody-Drug Conjugates
Early efforts to improve the anti-tumor efficacy of monoclonal antibodies were focused on boosting their cytotoxicity effects on the targeted cancer cells. For this purpose, the conjugation of warheads such as radioisotopes, toxins, enzymes or chemotherapeutics was the common strategy. Regardless of target, this approach yielded a multitude of molecular species with varying clinical efficacy. The limited success of these conjugates showcases the challenges of developing a highly toxic agent with acceptable pharmacokinetic and safety profiles. Unfortunately, although these drugs promise that low toxicity will be achieved through high specificity towards tumor antigens, these antigens are often more ubiquitous than specific.[2]
Historically, ADC therapies in clinical development have been limited by the fact that they are structurally heterogeneous populations in which the position and number of conjugated linkers and warheads vary significantly. Such heterogeneity prevents precise structure-based design, and therefore limits definition of structure-activity relationships (SARS). [3] [4][5]
At Sutro, we can incorporate novel non-natural amino acids (nnAA) at any site in an antibody structure, thereby allowing for single-species ADCs with site-specific conjugation of linker and warhead. Of vital importance in this process is Sutro’s ability to perform rapid and parallel synthesis of numerous variants, taking advantage of a substantial number of different sites and enabling analyses early in discovery to define SARs and locate the best positions for nnAA incorporation.
Best New Drug Developer
This year has certainly been a challenging one, and throughout the pandemic, our team has continued to work around the clock to avoid hurdles and overcome difficulties, while maintaining the progress of our programs and developmental pipeline with the ultimate goal of bringing live-saving solutions to patients.
The Best New Drug Developer award received at the World ADC Digital Event highlights the enormous potential of our ADC pipeline, STRO-001, STRO-002 and CC-99712. We are encouraged by our emerging and promising clinical data and the patient benefit that these product candidates may offer.
STRO-001
Our STRO-001 therapeutic candidate is a first-in-class and potentially best-in-class ADC directed against CD74, which is highly expressed in blood cancers involving B cell malignancies. STRO-001 was designed to directly target cancer cells and deliver a cytotoxic payload and it is currently undergoing investigation in a Phase I clinical trial for patients with advanced B-cell malignancies, which includes patients with multiple myeloma (MM) and non-Hodgkin lymphoma (NHL). There is a growing need for new treatment options for patients with multiple myeloma; in October 2018, we announced that STRO-001 was granted Orphan Drug Designation by the Food and Drug Administration (FDA) for this specific indication.
STRO-002
The second therapeutic candidate developed using our XpressCF+™ technology platform being evaluated in a clinical trial is STRO-002, a potentially best-in-class ADC, targeting folate receptor alpha (FolRα) a cell-surface protein highly expressed in gynecological cancers. Currently, STRO-002 is being investigated in a Phase I clinical trial of patients with ovarian and endometrial cancers. Recently, at the 2020 xDigital Annual Global Meeting of the International Gynecologic Cancer Society (IGCS), we presented new positive data that demonstrated the promising efficacy and safety profile of STRO-002 in a heavily pretreated patient population.
CC-99712
Our third program, CC-99712 (BCMA-targeting ADC), is part of our collaboration with Bristol Myers Squibb (via acquisition of Celgene Corporation). In this program, Bristol Myers Squibb is enrolling candidates for a Phase I clinical trial of patients with multiple myeloma. Sutro’s proprietary technology was responsible for the discovery and manufacturing of CC-99712, for which Bristol Myers Squibb has worldwide development and commercialization rights.
Sutro is dedicated to transforming the lives of cancer patients by creating therapeutics with improved profiles for clinical indications with high unmet need. This award acknowledges how Sutro’s team has been pushing the boundaries, dedicating their efforts to the pursuit of developing a novel way to fight cancer. We are extremely proud of the extraordinary teamwork of our company’s employees, which aims to contribute to the forefront of cancer research today.
Clinical trials
Study of STRO-001, an Anti-CD74 Antibody Drug Conjugate, in Patients With Advanced B-Cell Malignancies – NCT03424603
Study of STRO-002, an Anti-Folate Receptor Alpha (FolRα) Antibody Drug Conjugate in Ovarian & Endometrial Cancers – NCT03748186
References
[1] Cancer Facts & Figures 2015. American Cancer Society. Online. last accesses on November 5, 2020.
[2] Hoffmann RM, Coumbe BGT, Josephs DH, Mele S, Ilieva KM, Cheung A, Tutt AN, Spicer JF, Thurston DE, Crescioli S, Karagiannis SN. Antibody structure and engineering considerations for the design and function of Antibody Drug Conjugates (ADCs). Oncoimmunology. 2017 Nov 20;7(3):e1395127. doi: 10.1080/2162402X.2017.1395127. PMID: 29375935; PMCID: PMC5769674.
[3] Guha R. On exploring structure-activity relationships. Methods Mol Biol. 2013;993:81-94. doi: 10.1007/978-1-62703-342-8_6. PMID: 23568465; PMCID: PMC4852705.
[4] Wang L, Amphlett G, Blättler WA, Lambert JM, Zhang W. Structural characterization of the maytansinoid-monoclonal antibody immunoconjugate, huN901-DM1, by mass spectrometry. Protein Sci. 2005 Sep;14(9):2436-46. doi: 10.1110/ps.051478705. Epub 2005 Aug 4. PMID: 16081651; PMCID: PMC2253466.
[5] Schumacher D, Hackenberger CP, Leonhardt H, Helma J. Current Status: Site-Specific Antibody Drug Conjugates. J Clin Immunol. 2016 May;36 Suppl 1:100-7. doi: 10.1007/s10875-016-0265-6. Epub 2016 Mar 22. PMID: 27003914; PMCID: PMC4891387.
Featured Image: STRO-002, a potentially best-in-class ADC, targeting folate receptor alpha (FolRα) a cell-surface protein highly expressed in gynecological cancers. Image courtesy: © 2016 – 2020 Sutro Biopharma. Used with permission.
