Luveltamab Tazevibulin

- 32% objective response rate (ORR) in evaluable patients at the 5.2 mg/kg starting dose – the selected dose for randomized portion (Part 2) of ongoing registrational REFRαME-O1 trial - - These data confirm luvelta’s robust response rate in patients with late-stage ovarian cancer expressing a broad range of folate receptor alpha (FRα) - - Neutropenia well-managed; no new safety findings - - Luvelta is positioned for an Accelerated Approval application in mid-2027 - SOUTH SAN FRANCISCO, Calif., Dec. 10, 2024 (GLOBE NEWSWIRE) -- Sutro Biopharma, Inc. (Sutro or the Company) (NASDAQ: STRO), a clinical-stage oncology company pioneering site-specific and novel-format antibody drug conjugates (ADCs), today announced the selected dose from the dose-optimization portion (Part 1) of REFRαME-O1, the registration-directed trial of luveltamab tazevibulin (luvelta) in platinum-resistant ovarian cancer (PROC), following a meeting with the U.S. Food and Drug Administration (FDA). "The topline results confirm luvelta’s favorable safety and efficacy profile at the starting dose of 5.2 mg/kg, further supporting our confidence that it can improve clinical outcomes compared to chemotherapy in our ongoing registrational trial," said Anne Borgman, M.D., Sutro’s Chief Medical Officer. “Consistent response rates were observed in patients across all levels of FRα expression of 25% or greater, reconfirming luvelta's potential to expand the benefit of a targeted treatment to 8 out of 10 PROC patients." REFRαME-O1 (Part 1) REFRαME-O1 (Part 1) evaluated luvelta in patients with PROC with low, medium, and high FRα expression levels. This includes patients with ≥25% Tumor Proportion Score (TPS), defined as at least 25% of tumor cells expressing FRα, at any staining intensity. In the dose-optimization (Part 1), patients were randomized 1:1 to a 5.2 mg/kg with prophylactic pegfilgrastim (G-CSF) for 2 cycles followed by 4.3 mg/kg for subsequent cycles (5.2 mg/kg group), or a 4.3 mg/kg dose of luvelta for all cycles (4.3 mg/kg group). We plan to present additional data at future medical meetings. Topline Results from Evaluable Patients (5.2 mg/kg group; N = 25): Achieved an objective response rate (ORR) of 32%, which includes one partial response that confirmed post data extraction1Disease control rate of 96%Approximately half of the patients treated were ineligible for an approved FRα-targeting ADC88% of patients received prior bevacizumabGrade 3 or higher neutropenia occurred in 32% of patients, no febrile neutropenia “The clinical results from Part 1 of REFRαME-O1 provide compelling evidence that luvelta has the potential to be both first in class and best in class for patients who have low to medium expression of FRα. FRα is a validated target, and luvelta has the opportunity to reach more patients in need,” commented Bradley Monk, M.D., Florida Cancer Specialists and Research Institute; Director GOG Partners. “The topline safety profile of luvelta from Part 1 is encouraging. Neutropenia rates were low, highlighting successful management guidelines. Furthermore, the lack of serious ocular damage, pancytopenia, or Interstitial Lung Disease provide further confidence in our ability to treat a broad group of women with PROC with a focus on their overall wellbeing,” stated Wendel Naumann, M.D., Professor, Levine Cancer, Atrium Health/Wake Forest University, Charlotte, NC. REFRαME-O1 (Part 2) Registrational Trial REFRαME-O1 (Part 2) is an ongoing global registrational trial for patients with PROC, evaluating a 5.2 mg/kg dose with prophylactic pegfilgrastim (G-CSF) for the first two cycles followed by a 4.3 mg/kg dose for subsequent cycles. Part 2 will enroll approximately 500 patients, randomized 1:1 to luvelta or investigators’ choice of chemotherapy. Luvelta is positioned for an Accelerated Approval application in mid-2027. *1: Data as of Aug 16, 2024. About Luveltamab TazevibulinLuveltamab tazevibulin, abbreviated as “luvelta” and formerly known as STRO-002, is a FRα-targeting antibody-drug conjugate (ADC) designed to treat a broad range of patients with ovarian cancer, including those with lower FRα-expression who are not eligible for approved treatment options targeting FRα. Developed and manufactured with Sutro’s cell-free XpressCF® platform, luvelta is a homogeneous ADC with four hemiasterlin cytotoxins per antibody, precisely positioned to efficiently deliver to the tumor while ensuring systemic stability after dosing. REFRαME-O1, a Phase 2/3 registration-directed study for patients with platinum-resistant ovarian cancer is ongoing. The Company has another ongoing registration-directed trial, REFRαME-P1, for patients with CBF/GLIS acute myeloid leukemia, a rare subtype of pediatric cancer, as well as additional ongoing trials in patients with endometrial cancer, non-small cell lung cancer, and in combination with bevacizumab in patients with ovarian cancer. The U.S. Food and Drug Administration (FDA) has granted luvelta a Fast Track designation for Ovarian Cancer, as well as Orphan and Rare Pediatric Disease designations for CBF/GLIS Pediatric AML. About Sutro Biopharma Sutro Biopharma, Inc., is a clinical-stage company relentlessly focused on the discovery and development of precisely designed cancer therapeutics, to transform what science can do for patients. Sutro’s fit-for-purpose technology, including cell-free XpressCF®, provides the opportunity for broader patient benefit and an improved patient experience. Sutro has multiple clinical stage candidates, including luveltamab tazevibulin, or luvelta, a registrational-stage folate receptor alpha (FolRα)-targeting ADC in clinical studies. A robust pipeline, coupled with high-value collaborations and industry partnerships, validates Sutro’s continuous product innovation. Sutro is headquartered in South San Francisco. For more information, follow Sutro on social media @Sutrobio, or visit www.sutrobio.com. Forward-Looking StatementsThis 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, anticipated preclinical and clinical development activities, including enrollment and site activation; timing of announcements of clinical results, trial initiation, and regulatory filings; outcome of discussions with regulatory authorities; potential benefits of luvelta and the Company’s other product candidates and platform; potential business development and partnering transactions; and potential market opportunities for luvelta and the Company’s other 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 and the Company’s ability to successfully leverage Fast Track designation, the market size for the Company’s product candidates to be smaller than anticipated, 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.

- Expects to deliver three Investigational New Drug (IND) applications in next three years based on next-generation ADC technology - - Two new clinical trials, REFRαME-P1, a registration-enabling trial of luvelta for pediatric patients with rare leukemia, and REFRαME-L1, a Phase 2 trial of luvelta for patients with non-small cell lung cancer, are underway - - Sutro presented data from the Phase 1b study of luvelta in combination with bevacizumab at ESMO 2024 demonstrating a 56% response rate at the recommended Phase 2 dose of luvelta (4.3 mg/kg) - - As of September 30, 2024, Sutro had $388.3 million in cash, cash equivalents and marketable securities - SOUTH SAN FRANCISCO, Calif., Nov. 13, 2024 (GLOBE NEWSWIRE) -- Sutro Biopharma, Inc. (Sutro or the Company) (NASDAQ: STRO), a clinical-stage oncology company pioneering site-specific and novel-format antibody drug conjugates (ADCs), today reported its financial results for the third quarter of 2024 and its recent business highlights. With its lead program, luveltamab tazevibulin (luvelta), Sutro recently initiated a registrational trial for a rare form of pediatric leukemia, a clinical trial for non-small cell lung cancer (NSCLC), and presented expansion data in combination with bevacizumab. The randomized portion of Sutro’s registrational trial for patients with advanced ovarian cancer is underway. Sutro expects to provide an update following alignment with the U.S. Food & Drug Administration (FDA) on the selected dose for the pivotal portion of this trial around the end of the year. Recognizing the potential patient benefit and commercial opportunity for luvelta, Sutro engaged Lazard to assist in its efforts to identify a partner for luvelta who can provide financial resources and expertise for the multi-indication development and commercialization of luvelta. Additionally, Sutro showcased at a recent Research Forum a portfolio of emerging next-generation ADCs, made possible by our unique cell-free platform, which are expected to drive value creation beyond luvelta. During the event, Sutro announced three planned IND filings over the next three years for wholly owned programs, including STRO-004, a tissue-factor targeting ADC, featuring a DAR8 exatecan payload and site-specific linker design, which is expected to enter the clinic next year. Recent Business Highlights and Select Anticipated Milestones Luveltamab Tazevibulin (luvelta), FRα-Targeting ADC Franchise: Sutro presented updated data from the Phase 1b study of luvelta in combination with bevacizumab for patients with ovarian cancer in a poster presentation at the European Society for Medical Oncology (ESMO) Congress 2024, demonstrating a 56% response rate at the recommended Phase 2 dose of luvelta (4.3 mg/kg) for this study. An expansion study of this combination is ongoing, with data expected in the first half of 2025.Part 2 (randomized portion) of the Phase 3 trial, REFRαME-O1, for treatment of platinum-resistant ovarian cancer (PROC), is ongoing.REFRαME-P1, a registration-enabling trial for pediatric patients with CBFA2T3::GLIS2 (CBF/GLIS; RAM phenotype) AML, is underway.A Phase 2 trial for the treatment of NSCLC is underway, with initial data expected in 2025. Additional Pipeline Development and Collaboration Updates: In October 2024, Sutro hosted a Research Forum highlighting next-generation ADC innovation and near-term pipeline milestones, including: STRO-004, a tissue factor-targeting ADC, which features a drug-antibody-ratio (DAR) of eight exatecan payloads and site-specific linker design, demonstrated greater anti-tumor activity and lower toxicities than a tissue factor benchmark ADC in preclinical models. Sutro anticipates filing an IND for STRO-004 in the second half of 2025.Dual-payload ADCs (ADC2) provide therapeutic benefits compared to standard ADCs, including potential to overcome tumor resistance mechanisms, and show increased anti-tumor activity and desirable properties in preclinical models.iADCs provide a novel mechanism of action, bridging innate and adaptive immunity to enable broad protection in a single molecule, and show increased and durable anti-tumor activity in a preclinical model compared to standalone ADCs or immune-stimulating antibody conjugates.Sutro’s proprietary and partnered preclinical ADC portfolio has potential across a broad range of tumor types and the Company plans to deliver three INDs over the next three years. Sutro continues to seek to maximize the value of its proprietary cell-free platform by working with partners on programs in multiple disease spaces and geographies and has generated from collaborators an aggregate of approximately $975 million in payments through September 30, 2024, including equity investments. Upcoming Events: Sutro plans to participate in three upcoming investor conferences. Webcasts of the presentations will be accessible through the News & Events page of the Investor Relations section of the Company’s website at www.sutrobio.com. Archived replays will be available for at least 30 days after the events. Jefferies London Healthcare Conference, November 19-21, 2024, in LondonThe Citizens JMP Hematology and Oncology Summit, December 2, 2024, VirtualPiper Sandler 36th Annual Healthcare Conference, December 3-5, 2024, in New York Third Quarter 2024 Financial Highlights Cash, Cash Equivalents and Marketable Securities As of September 30, 2024, Sutro had $388.3 million in cash, cash equivalents and marketable securities. Realized Gain on Sale of Vaxcyte Common StockIncluded in non-operating interest and other income (expense), net, on the Statement of Operations for the nine months ended September 30, 2024 was a realized gain of $32.1 million from the sale of approximately 0.7 million shares of Vaxcyte common stock, with net proceeds of approximately $74.0 million. As of September 30, 2024, Sutro does not hold any shares of Vaxcyte common stock. RevenueRevenue was $8.5 million for the quarter ended September 30, 2024, as compared to $16.9 million for the same period in 2023, with the 2024 amount related principally to the Astellas collaboration and the Vaxcyte agreement. Future collaboration and license revenue under existing agreements, and from any additional collaboration and license partners, will fluctuate as a result of the amount and timing of revenue recognition of upfront, milestones, and other agreement payments. Operating ExpensesTotal operating expenses for the quarter ended September 30, 2024 were $76.4 million, as compared to $60.9 million for the same period in 2023. The 2024 quarter includes non-cash expenses for stock-based compensation of $6.5 million and depreciation and amortization of $1.8 million, as compared to $6.0 million and $1.7 million, respectively, in the comparable 2023 period. Total operating expenses for the quarter ended September 30, 2024 were comprised of research and development expenses of $62.1 million and general and administrative expenses of $14.3 million. About Sutro BiopharmaSutro Biopharma, Inc., is a clinical-stage company relentlessly focused on the discovery and development of precisely designed cancer therapeutics, to transform what science can do for patients. Sutro’s fit-for-purpose technology, including cell-free XpressCF®, provides the opportunity for broader patient benefit and an improved patient experience. Sutro has multiple clinical stage candidates, including luveltamab tazevibulin, or luvelta, a registrational-stage folate receptor alpha (FolRα)-targeting ADC in clinical studies. A robust pipeline, coupled with high-value collaborations and industry partnerships, validates Sutro’s continuous product innovation. Sutro is headquartered in South San Francisco. For more information, follow Sutro on social media @Sutrobio, or visit www.sutrobio.com. 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, anticipated preclinical and clinical development activities, including enrollment and site activation; timing of announcements of clinical results, trial initiation, and regulatory filings; outcome of discussions with regulatory authorities; potential benefits of luvelta and the Company’s other product candidates and platform; potential business development and partnering transactions; potential market opportunities for luvelta and the Company’s other product candidates; and the Company’s expected cash runway. 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 and the Company’s ability to successfully leverage Fast Track designation, the market size for the Company’s product candidates to be smaller than anticipated, 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. Sutro Biopharma, Inc.Selected Statements of Operations Financial Data(Unaudited)(In thousands, except share and per share amounts) Three Months EndedNine Months Ended September 30,September 30, 2024 2023 2024 2023 Revenues$8,520 $16,924 $47,234 $40,010 Operating expenses Research and development 62,108 45,669 181,006 126,660 General and administrative 14,331 15,269 39,423 45,780 Total operating expenses 76,439 60,938 220,429 172,440 Loss from operations (67,919) (44,014) (173,195) (132,430)Interest income 4,875 4,550 13,882 9,952 Unrealized gain on equity securities - 694 - 2,023 Non-cash interest expense related to thesale of future royalties (7,910) (5,936) (22,380) (6,378)Interest and other income (expense), net 22,167 (2,739) 26,683 (8,640)Loss before provision for income taxes (48,787) (47,445) (155,010) (135,473)Provision for income taxes - 1,839 8 2,385 Net loss$(48,787) $(49,284) $(155,018) $(137,858)Net loss per share, basic and diluted$(0.59) $(0.81) $(2.07) $(2.30)Weighted-average shares used in computingbasic and diluted loss per share 82,043,671 60,599,025 74,934,737 59,894,181 Sutro Biopharma, Inc.Selected Balance Sheets Financial Data(Unaudited)(In thousands) September 30,2024(1) December 31,2023(2) Assets Cash, cash equivalents and marketable securities$388,254 $333,681 Investment in equity securities - 41,937 Accounts receivable 6,655 36,078 Property and equipment, net 18,997 21,940 Operating lease right-of-use assets 19,027 22,815 Other assets 18,899 14,285 Total Assets$451,832 $470,736 Liabilities and Stockholders’ Equity Accounts payable, accrued expenses and other liabilities$53,222 $64,293 Deferred revenue 90,559 74,045 Operating lease liability 24,864 29,574 Debt - 4,061 Deferred royalty obligation related to the sale of future royalties 171,967 149,114 Total liabilities 340,612 321,087 Total stockholders’ equity 111,220 149,649 Total Liabilities and Stockholders’ Equity$451,832 $470,736 (1) The condensed balance sheet as of September 30, 2024 was derived from the unaudited financial statements included in the Company's Quarterly Report on Form 10-Q for the quarter ended September 30, 2024, filed with the Securities and Exchange Commission on November 13, 2024. (2) The condensed balance sheet as of December 31, 2023 was derived from the unaudited financial statements included in the Company's Annual Report on Form 10-K for the year ended December 31, 2023, filed with the Securities and Exchange Commission on March 25, 2024.