Trastuzumab CRD 5500 conjugate (Curadev Pharma)

SOUTH SAN FRANCISCO, Calif., Jan. 21, 2021 /PRNewswire/ -- Sutro Biopharma, Inc.. (NASDAQ: STRO), a clinical-stage drug discovery, development and manufacturing company focused on the application of precise protein engineering and rational design to create next-generation cancer and autoimmune therapeutics, today announced the dosing of the first patient in the dose-expansion cohort of the Phase 1 STRO-002 study. STRO-002 is an internally developed, folate receptor alpha (FolRα) targeting antibody-drug conjugate (ADC) for the potential treatment of ovarian cancer. The dose-expansion cohort will assess the efficacy, safety and tolerability of STRO-002 at 4.3 and 5.2 mg/kg, given every 3 weeks in patients with ovarian cancer. The dose-expansion cohort for FolRα-selected endometrial cancer is planned for later this year. "We are pleased to advance the clinical development of STRO-002 into dose-expansion studies. Results from our STRO-002 dose escalation in a heavily pre-treated ovarian cancer patient population demonstrated improved outcomes in RECIST response and duration of response," said Dr. Arturo Molina, Chief Medical Officer of Sutro Biopharma. "Sutro plans to expand the study to approximately 35 clinical sites in the U.S. and Europe. We are hopeful that the dose-expansion study will validate the preliminary signs of efficacy we have seen in dose-escalation and provide valuable data on the treatment paradigm and patient population that will benefit from treatment, bringing us one step closer to offering an important new potential treatment option to ovarian cancer patients." Dr. Lainie Martin, Leader of Gynecology/Oncology Program at Hospital of the University of Pennsylvania and an investigator on the STRO-002-GM1 study, said, "STRO-002 continues to be well-tolerated and we have observed encouraging preliminary activity in patients with advanced platinum-resistant and refractory ovarian cancer. We are excited to be part of the STRO-002-GM1 dose-expansion study and to provide additional clinical data to show the potential of this therapeutic for ovarian patients with limited treatment options." The dose-expansion study includes two patient cohorts, advanced epithelial ovarian cancer and endometrial cancer. The ovarian cancer cohort currently enrolling includes patients with platinum resistant disease and have received 1-3 prior regimens or platinum sensitive patients that have received 2-3 prior treatment regimens. Patients in the dose-expansion cohort of the STRO-002-GM1 Phase 1 study will be randomized 1:1 and treated with either 4.3 or 5.2 mg/kg STRO-002 intravenously once every three-weeks. Patients will not be pre-selected for FolRα expression and fresh or archival tumor tissue sample is required for immunohistochemistry (IHC) analysis of FolRα expression. Additional information on the study can be found at: About the Phase 1 Trial of STRO-002 in Ovarian Cancer STRO-002-GM1, the Phase 1 open-label, multicenter, dose escalation trial with dose expansion of STRO–002, has completed enrollment. Follow-up is ongoing and will continue to evaluate the safety, tolerability, and preliminary anti-tumor activity of STRO-002 in adults with advanced epithelial ovarian cancer, including fallopian and primary peritoneal cancer. The trial is registered with clinicaltrials.gov identifier NCT03748186. Sutro discovered, developed and manufactures STRO-002 using its proprietary XpressCF® cell-free protein synthesis and XpressCF+™ site-specific conjugation technologies. About Sutro Biopharma Sutro Biopharma, Inc., located in South San Francisco, is a clinical-stage drug discovery, development and manufacturing company. Using precise protein engineering and rational design, Sutro is advancing next-generation oncology therapeutics. Sutro's proprietary and integrated cell-free protein synthesis platform XpressCF® and site-specific conjugation platform XpressCF+™ led to the discovery of STRO-001 and STRO-002, Sutro's first two internally-developed ADCs. STRO-001 is a CD74-targeting ADC currently being investigated in a Phase 1 clinical trial of patients with advanced B-cell malignancies, including multiple myeloma and non-Hodgkin lymphoma. STRO-001 was granted Orphan Drug Designation by the FDA for multiple myeloma in October 2018. STRO-002 is a folate receptor alpha (FolRα)-targeting ADC, currently being investigated in a Phase 1 clinical trial of patients with ovarian and endometrial cancers. This is the second product candidate to be evaluated in clinical trials resulting from Sutro's XpressCF® and XpressCF+™ technology platforms. A third program, CC-99712 (BCMA-targeting ADC), which is part of Sutro's collaboration with Bristol Myers Squibb (formerly Celgene Corporation), is enrolling patients for its Phase 1 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 entitled to development and regulatory milestone payments and tiered royalties from Bristol Myers Squibb for this BCMA ADC. Sutro is dedicated to transforming the lives of cancer patients by creating medicines with improved therapeutic profiles for areas of unmet need. To date, Sutro's platform has led to cytokine-based immuno-oncology therapies, ADCs, vaccines and bispecific antibodies directed at precedented targets in clinical indications where the current standard of care is suboptimal. The platform allows it to accelerate discovery and development of potential first-in-class and best-in-class molecules through rapid and systematic evaluation of protein structure-activity relationships to create optimized homogeneous product candidates. In addition to developing its own oncology pipeline, Sutro is collaborating with select pharmaceutical and biotech companies to discover and develop novel, next-generation therapeutics. As the pace of clinical development accelerates, Sutro and its partners are developing therapeutics designed to more efficiently kill tumors without harming healthy cells. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements the Company makes regarding anticipated preclinical and clinical development activities, timing of clinical trials and announcements of clinical results, potential benefits of the Company's product candidates and platform and potential market opportunities for the Company's product candidates. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. Although the Company believes that the expectations reflected in such forward-looking statements are reasonable, the Company cannot guarantee future events, results, actions, levels of activity, performance or achievements, and the timing and results of biotechnology development and potential regulatory approval is inherently uncertain. Forward-looking statements are subject to risks and uncertainties that may cause the Company's actual activities or results to differ significantly from those expressed in any forward-looking statement, including risks and uncertainties related to the Company's ability to advance its product candidates, the receipt and timing of potential regulatory designations, approvals and commercialization of product candidates, the impact of the COVID-19 pandemic on the Company's business, clinical trial sites, supply chain and manufacturing facilities, the Company's ability to maintain and recognize the benefits of certain designations received by product candidates, the timing and results of preclinical and clinical trials, the Company's ability to fund development activities and achieve development goals, the Company's ability to protect intellectual property, and the Company's commercial collaborations with third parties and other risks and uncertainties described under the heading "Risk Factors" in documents the Company files from time to time with the Securities and Exchange Commission. These forward-looking statements speak only as of the date of this press release, and the Company undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date hereof. Investor Contacts Annie J. Chang Sutro Biopharma (650) 801-5728 ajchang@sutrobio.com Company Codes: NASDAQ-NMS:STRO

William J. (Bill) Newell, Sutro Chief Executive Officer, pictured above. Photo Courtesy of Sutro Biopharma Sutro Biopharma wants to use its antibody-drug conjugates (ADCs) as “laser-guided weapons” against cancer cells while sparing the surrounding ones and therefore patients’ quality of life. “I like to think of antibody-drug conjugates as kind of laser-guided weapons against tumor cells. And then what we can do, and Sutro is very focused on this, is make certain that once the very potent cytotoxin does its job inside the tumor cell, that it is not as damaging to surrounding healthy cells as maybe a chemotherapy would be,” said Sutro Chief Executive Officer, William J. (Bill) Newell. To that end, you would be hard-pressed to find a biopharma company that has had a more successful second half of 2020 than Sutro, which is leveraging its scalable cell-free protein synthesis platform to develop best-in-class homogeneous molecules for oncology therapeutics. On December 4th, Sutro announced promising interim data from a Phase I dose-escalation study of STRO-002, one of its first two internally developed ADCs, in ovarian cancer. Of the 31 trial participants evaluable for RECIST responses, one patient obtained a complete response (CR) and nine achieved a partial response (PR), while 23 patients achieved disease control at 12 weeks. The patients were treated with clinically active dose levels at 2.9 mg/kg or higher. “We were very pleased to see the patient responses in a very heavily pre-treated patient population. Many of these women had been through six lines of prior therapy and frankly, without our trial, would have been on palliative care for the remainder of their lives,” Newell said. “We were thrilled to see that of the 31 women who were treated at therapeutically relevant doses, four of those women so far have been on our study drug for over a year, which is remarkable given the advanced state of their disease. And large numbers of women have been on our drug for over 4 months, so that’s a very good indicator that your drug is active and controlling the patient disease,” Newell said. Newell said that he looks forward to sharing data from a follow-up trial recently launched looking at two different dose levels they feel are optimal for long term disease control, which Sutro plans to report on during the second half of 2021. Results like these are what motivated Newell to leave a successful law practice for the much different pastures of biotech, which he described as “a robust industry, and one that I felt an affinity to. Not because I have a scientific background, but because it resonated with me as to what the mission of the industry was. And I felt like if I could contribute to that mission, it would be a good way to spend the next part of my career.” Once established in the industry, Sutro’s proprietary and integrated cell-free protein synthesis and site-specific conjugation platforms, XpressCF® and XpressCF+™, are what drew Newell to the company. “Imagine a technology that allows you to make vaccines, that allows you to make antibody-drug conjugates, bi-specific antibodies, bi-specific antibody-drug conjugates, cytokine derivatives, and more. It gives you a lot of opportunities to develop new and different therapeutics and vaccines. And I could see that the technology had that potential even back in 2009.” While conventional methods for expressing proteins make use of cell lines originating from bacteria, yeast, insects, plants, or mammals, Sutro’s technology platform is enabled by the separation, into an extract, of the cellular components necessary to produce proteins, from the protein process generation itself. This cell-free technology allows for a more flexible platform where a single protein can be rapidly scaled-up, and a single master cell bank used for extract generation can provide the manufacturing platform for multiple different proteins, allowing for accelerated development. Ultimately, this could lead to the accelerated realization of critical weapons against cancer. While Sutro’s technological platform opens multiple therapeutic doors, the company’s singular focus on homogeneous molecules is a key part of its competitive strategy. “There is no heterogeneity. That’s not a hallmark of our technology, and that allows us to rapidly compete different homogeneous molecules to understand which one is the optimal one to move forward to the clinic,” explained Newell. “We think it’s much better to identify the single species that is optimal and put your development resources behind that single species. So, that’s what we do. We only make a single species, much the way a small molecule is one single species as well, and we think that gives our molecules a competitive advantage.” Another important part of Sutro’s commitment to quality is the development of symbiotic partnerships. “A lot of biotech companies develop a molecule and then they look to partner that molecule. We were looking for something different. We look for a partner that has a deep understanding of cancer biology and targets, but may not have all the tools that we have in order to develop an optimized molecule. So, there’s this tremendous synergy between their understanding of the tumor microenvironment and our ability to rapidly iterate the research efforts and really synergize the research of the two organizations,” Newell said. Sutro is developing CC99712, a BCMA-Targeting ADC against Multiple Myeloma with Bristol Myers Squibb, M1231, a MUC1-EGFR Bispecific ADC with EMD Serono, and Cytokine Derivatives in the oncology and autoimmune spaces with Merck & Co. Sutro’s other internally developed ADC, STRO-001, a CD74-Targeting ADC, is currently being tested in an ongoing dose-escalation study for therapeutic use in Multiple Myeloma and Non-Hodgkin’s lymphoma. Sutro presented interim data from the study at the 62nd American Society of Hematology Annual Meeting (ASH), which showed one CR two 2 PRs, as well as a strong safety profile with 90% of treatment-emergent adverse events (TEAEs) being at either grade one or two. Newell stated that Sutro expects to report on a “more complete data set at the more therapeutically meaningful dose levels in both myeloma and Non-Hodgkin’s lymphoma” in the May or June 2021 timeframe. CD74 was Sutro’s initial target of choice, and Newell explained the rationale behind this decision. “We like that target because it is probably one of the most rapid internalizing antigens expressed by any type of cancer cell. So what that means is, as soon as our antibody-drug conjugate finds its way to the surface of the tumor cell, it gets rapidly internalized and that means we’re effective once we bind in terms of getting the cytotoxic payload where we want it to be,” he said. Looking ahead to 2021, Newell said that Sutro is actively developing new molecules and programs: “We don’t lack for ideas, and I think we’re fairly well capitalized at this point to pursue multiple different modalities. I think what separates Sutro from a lot of other companies is that we don’t just have one trick. We’re constantly looking at different modalities and different targets.” While he would not give specifics prior to a set path to the clinical development arena, Newell said that “you can rest assured, we’re looking at many different programs in 2021, and excited to talk about that as they mature.” Newell believes that the overall oncology therapeutics landscape is in a state of rapid development. “I think we’re doing more today, and over the next 1-3 years, you’ll see many new more approaches to cancer that have better patient outcomes in terms of extending life and controlling the tumor,” he said. “What we’d like to see more of is that, with good tolerability for patients. That’s what Sutro is focused on: Delivering an impactful therapeutic that is also better tolerated, so that the patient can have a better quality of life while they enjoy hopefully a longer life as well.”