Plus Therapeutics(PSTV) - 2020 Q4 - Annual Report

FORM 10-K Filing Information Filing Details This document is an Annual Report on Form 10-K for the fiscal year ended December 31, 2020, filed by PLUS THERAPEUTICS, INC. (formerly Cytori Therapeutics, Inc.), with common stock traded on the Nasdaq Capital Market under the symbol PSTV - The filing is an Annual Report on Form 10-K for the fiscal year ended December 31, 2020[2] - The registrant's name is PLUS THERAPEUTICS, INC., previously known as Cytori Therapeutics, Inc.[2] Common Stock Trading Details | Title of each class | Trading Symbol(s) | Name of each exchange on which registered | | :------------------ | :---------------- | :---------------------------------------- | | Common Stock, par value $0.001 per share | PSTV | Nasdaq Capital Market | Registrant Status The registrant is not a well-known seasoned issuer, is not required to file reports under Section 13 or 15(d) of the Exchange Act, has filed all required reports in the preceding 12 months, and has submitted all Interactive Data Files, classified as a Non-Accelerated Filer and a Smaller Reporting Company - The registrant is not a well-known seasoned issuer and is not required to file reports pursuant to Section 13 or 15(d) of the Exchange Act[3] - The registrant has filed all required reports during the preceding 12 months and has submitted electronically every Interactive Data File[3] - The registrant is classified as a Non-Accelerated Filer and a Smaller Reporting Company[3] Cautionary Statement Regarding Forward-Looking Statements This report contains forward-looking statements based on management's assumptions about future activities, events, and developments, subject to various risks and uncertainties including product candidate stages, clinical trial outcomes, liquidity, regulatory approvals, competition, and capital raising, with readers cautioned to review the "Risk Factors" section - The report contains forward-looking statements based on management's assumptions about future activities, events, or developments[8] - Actual results may differ materially due to factors such as the early stage of product candidates, clinical trial uncertainties, liquidity, regulatory risks, market conditions, and competition[9] - Readers are advised to carefully read the "Risk Factors" section and not to place undue reliance on forward-looking statements, which speak only as of the report date[10] Risk Factor Summary This section summarizes principal factors that could adversely affect the company's business, financial condition, and results of operations, including recurring losses, the need for substantial additional funding, global capital market volatility, a "going concern" emphasis from auditors, and intense competition in the life science industry - The company has incurred losses since inception and expects significant net losses, potentially never becoming profitable[14] - Substantial additional funding is required for product development, future operations, and debt repayment; inability to secure funds may lead to delays or cessation of operations[14] - The audit report includes an emphasis paragraph regarding substantial doubt about the company's ability to continue as a "going concern"[14] PART I Item 1. Business Plus Therapeutics is a clinical-stage pharmaceutical company focused on developing innovative treatments for rare and difficult-to-treat cancers, particularly those of the central nervous system, leveraging a nanoscale drug development platform with RNL™ as its lead candidate for recurrent glioblastoma, and a business strategy involving internal drug redesign, manufacturing, non-clinical analyses, early-stage clinical trials, and partnering for late-stage development and commercialization - Plus Therapeutics focuses on developing innovative treatments for rare and difficult-to-treat cancers, especially central nervous system cancers[16] - The company utilizes a nanoscale drug development platform and has an established, GMP-validated R&D and manufacturing facility in San Antonio, TX[17] - The business model includes market mapping, internal drug redesign, in-house manufacturing, non-clinical analyses, early-stage clinical trials, and partnering for late-stage development and commercial launch[18] Pipeline Plus Therapeutics has four investigational drugs, with three in clinical stages: Rhenium NanoLiposomes (RNL™) for recurrent glioblastoma (rGBM), DocePLUS™ for solid tumors, and DoxoPLUS™ for ovarian cancer, with RNL™ as the lead candidate showing early efficacy signals in Phase 1 trials and receiving Orphan Drug and Fast Track designations from the FDA - Plus Therapeutics has four investigational drugs, with three in clinical stages: RNL™ (recurrent glioblastoma), DocePLUS™ (solid tumors), and DoxoPLUS™ (ovarian cancer)[19][24] - RNL™ is a patented radiotherapy for recurrent glioblastoma, currently in a U.S. NCI-supported Phase 1 dose-finding clinical trial (ReSPECT™)[24][27] - RNL™ has demonstrated early potential efficacy signals, with two patients surviving over 30 months compared to a median of 9 months for standard care, and received FDA Orphan Drug and Fast Track designations in September 2020[27][28] Licensing On March 29, 2020, Plus Therapeutics entered an exclusive license agreement with NanoTx, Corp. for global rights to develop and commercialize radiolabeled nanoliposomes, including RNL™, involving an upfront payment of $400,000 cash and $300,000 in stock, with potential future milestone payments up to $136.5 million and tiered single-digit royalties on U.S. and European sales, for technology developed by a multi-institutional consortium and supported by an active $3M NIH/NCI award - Plus Therapeutics licensed radiolabeled nanoliposome technology, including RNL™, from NanoTx, Corp. on March 29, 2020, for global development and commercialization[29][32] NanoTx License Agreement Terms | Payment Type | Amount | | :------------- | :----- | | Upfront Cash | $400,000 | | Upfront Equity | $300,000 | | Potential Development & Sales Milestones | Up to $136.5 million | | Royalties | Tiered single-digit on U.S. and European sales | - The licensed technology was developed by a Texas-based multi-institutional consortium and is supported by an active $3M NIH/NCI award for RNL's clinical development[33] Manufacturing The company operates a dedicated nanoparticle R&D and commercial-scale manufacturing facility in San Antonio, Texas, designed to comply with cGMP for drug candidates, enabling cost-effective production and process control, and also entered a Master Services Agreement with Piramal Pharma Solutions, Inc. in January 2021 for the development, manufacture, and supply of RNL-Liposome Intermediate Drug Product - Plus Therapeutics has a dedicated nanoparticle R&D and commercial-scale manufacturing facility in San Antonio, Texas, compliant with cGMP for drug candidates[34] - The facility enables cost-effective drug substance production and control over the manufacturing process[34] - A Master Services Agreement was signed with Piramal Pharma Solutions, Inc. on January 8, 2021, for the development, manufacture, and supply of RNL-Liposome Intermediate Drug Product[34] Competition Plus Therapeutics competes based on the safety and efficacy of its therapies, brand, pricing, clinical data, regulatory approvals, and reimbursement, with success dependent on developing platforms, advancing clinical programs, securing approvals, expanding commercial footprint, producing high-quality products, achieving economies of scale, protecting IP, retaining talent, and executing partnerships, while RNL™ faces competition in recurrent glioblastoma from numerous companies with drug development programs at various clinical stages - Competition is based on safety, efficacy, brand, pricing, clinical data, regulatory approvals, and reimbursement[35] - Success depends on developing platforms, advancing clinical programs, securing regulatory approvals, expanding commercial footprint, producing high-quality products, achieving economies of scale, protecting intellectual property, hiring/retaining talent, and executing partnerships[36] - RNL™ faces competition in recurrent glioblastoma from numerous companies including Bayer, VBL Therapeutics, Kintara Therapeutics, and Novartis, all with drug development programs at various clinical stages[35] Intellectual Property The company's success relies on protecting its proprietary technology through patents, trade secrets, copyrights, trademarks, and confidentiality agreements, with RNL™ covered by U.S. Patent No. 7,718,160 (expiring December 2026, potential 5-year extension) and a provisional application (filed November 2020, potential expiry 2041) for methods of use, while DocePLUS is covered by U.S. Patent No. 7,179,484 (expiring **April 2