[PART I FINANCIAL INFORMATION](index=4&type=section&id=PART%20I%20FINANCIAL%20INFORMATION) [Item 1. Financial Statements](index=4&type=section&id=Item%201.%20Financial%20Statements) Unaudited H1 2021 financials show increased assets, a **$5.5 million net loss**, and raise going concern doubts [Consolidated Condensed Balance Sheets](index=4&type=section&id=Consolidated%20Condensed%20Balance%20Sheets) As of June 30, 2021, cash, total assets, and equity significantly increased due to stock issuances Balance Sheet Summary (in thousands) | Metric | June 30, 2021 | December 31, 2020 | | :--- | :--- | :--- | | **Assets** | | | | Cash and cash equivalents | $17,161 | $8,346 | | Total current assets | $18,001 | $9,175 | | Total assets | $20,834 | $12,105 | | **Liabilities & Equity** | | | | Total current liabilities | $8,354 | $8,539 | | Total liabilities | $8,889 | $9,074 | | Total stockholders' equity | $11,945 | $3,031 | [Consolidated Condensed Statements of Operations](index=5&type=section&id=Consolidated%20Condensed%20Statements%20of%20Operations) Net losses for Q2 and H1 2021 increased to **$2.8 million** and **$5.5 million**, driven by higher R&D expenses Statement of Operations Highlights (in thousands, except per share data) | Metric | Q2 2021 | Q2 2020 | H1 2021 | H1 2020 | | :--- | :--- | :--- | :--- | :--- | | Development revenues | $0 | $185 | $0 | $303 | | Research and development | $1,106 | $327 | $2,233 | $1,268 | | General and administrative | $1,469 | $1,429 | $2,821 | $3,047 | | Loss from operations | $(2,575) | $(2,352) | $(5,054) | $(4,793) | | Net loss | $(2,800) | $(1,839) | $(5,520) | $(2,926) | | Net loss per share | $(0.25) | $(0.45) | $(0.56) | $(0.74) | [Consolidated Condensed Statements of Stockholders' Equity](index=6&type=section&id=Consolidated%20Condensed%20Statements%20of%20Stockholders'%20Equity) Stockholders' equity increased to **$11.9 million** by June 30, 2021, from stock sales and warrant exercises, offset by net loss - During the first half of 2021, the company raised approximately **$7.1 million** from the sale of common stock, net of offering costs, and an additional **$2.0 million** from the exercise of warrants[18](index=18&type=chunk) - In the second quarter of 2021, an additional **$5.1 million** was raised from the sale of common stock, net of offering costs[18](index=18&type=chunk) [Consolidated Condensed Statements of Cash Flows](index=7&type=section&id=Consolidated%20Condensed%20Statements%20of%20Cash%20Flows) H1 2021 saw **$5.4 million** net cash used in operations, offset by **$14.3 million** from financing, increasing cash to **$17.2 million** Cash Flow Summary for the Six Months Ended June 30 (in thousands) | Metric | 2021 | 2020 | | :--- | :--- | :--- | | Net cash used in operating activities | $(5,405) | $(2,911) | | Net cash used in investing activities | $(80) | $(423) | | Net cash provided by (used in) financing activities | $14,300 | $(4,992) | | **Net increase (decrease) in cash** | **$8,815** | **$(8,326)** | - Financing activities in H1 2021 included **$12.3 million** in net proceeds from the sale of common stock and **$2.0 million** from the exercise of warrants[20](index=20&type=chunk) [Notes to Consolidated Condensed Financial Statements](index=8&type=section&id=Notes%20to%20Consolidated%20Condensed%20Financial%20Statements) Notes detail accounting policies, liquidity concerns raising substantial doubt about going concern due to recurring losses - The company incurred a net loss of **$5.5 million** for the six months ended June 30, 2021, and had an accumulated deficit of **$439.0 million**, raising substantial doubt about its ability to continue as a going concern[28](index=28&type=chunk) - The company raised **$6.3 million** (net) through its At-the-Market (ATM) agreement with Canaccord and **$6.0 million** (net) through its purchase agreement with Lincoln Park during the first six months of 2021[30](index=30&type=chunk)[31](index=31&type=chunk) - On June 22, 2021, the company was named as a defendant in a lawsuit by Lorem Vascular, Pte. Ltd., which is seeking at least **$6.0 million** in damages, though the company believes the claims are without merit[58](index=58&type=chunk) [Item 2. Management's Discussion and Analysis of Financial Condition and Results of Operations](index=17&type=section&id=Item%202.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) Management discusses clinical-stage drug development, increased R&D, precarious liquidity, and reliance on recent financing [Overview and Pipeline](index=17&type=section&id=Overview%20and%20Pipeline) Plus Therapeutics focuses on its RNL nanotechnology platform for rGBM, currently in Phase 1 trials with FDA designations - The company's lead drug, Rhenium NanoLiposomes (RNL), is being developed for recurrent glioblastoma (rGBM) and is supported by a **$3 million** award from NIH/NCI[86](index=86&type=chunk) - RNL is currently in a Phase 1 dose-finding clinical trial (ReSPECT™), which has completed its seventh dose escalation cohort and is proceeding to an eighth cohort with a **40% increase** in drug volume and radiation dose[92](index=92&type=chunk) - In September 2020, the FDA granted both Orphan Drug and Fast Track designations to RNL for the treatment of glioblastoma[93](index=93&type=chunk) [Results of Operations](index=20&type=section&id=Results%20of%20Operations) Q2 and H1 2021 saw no revenue, significant increases in R&D expenses for RNL development, and stable G&A Research and Development Expenses (in thousands) | Period | 2021 | 2020 | Change | | :--- | :--- | :--- | :--- | | Three Months Ended June 30 | $1,106 | $327 | +$779 | | Six Months Ended June 30 | $2,233 | $1,268 | +$965 | - The increase in R&D expenses for both the three and six-month periods was primarily due to increased expenditures related to the development of RNL in compliance with cGMP requirements[101](index=101&type=chunk) - General and administrative expenses decreased by **$0.2 million** for the six months ended June 30, 2021, compared to 2020, mainly due to a **$0.6 million** reduction in legal expenses, offset by increases in stock-based compensation and consulting services[104](index=104&type=chunk) [Liquidity and Capital Resources](index=22&type=section&id=Liquidity%20and%20Capital%20Resources) Liquidity raises going concern doubt, relying on **$12.3 million** in H1 2021 equity financing to offset losses Key Liquidity Measures (in thousands) | Metric | June 30, 2021 | Dec 31, 2020 | | :--- | :--- | :--- | | Cash and cash equivalents | $17,161 | $8,346 | | Working capital | $9,647 | $636 | - During H1 2021, the company issued **2,179,193 shares** under its ATM agreement for net proceeds of **$6.3 million**, exhausting the program[114](index=114&type=chunk) - During H1 2021, the company issued **2,262,686 shares** under its purchase agreement with Lincoln Park for net proceeds of **$6.0 million**[115](index=115&type=chunk) [Item 3. Quantitative and Qualitative Disclosures about Market Risk](index=24&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20about%20Market%20Risk) The company states that quantitative and qualitative disclosures about market risk are not applicable - The company has determined that quantitative and qualitative disclosures about market risk are not applicable[129](index=129&type=chunk) [Item 4. Controls and Procedures](index=24&type=section&id=Item%204.%20Controls%20and%20Procedures) Management concluded that disclosure controls and procedures were effective as of June 30, 2021, with no material changes to internal control over financial reporting - The CEO and CFO concluded that the company's disclosure controls and procedures were effective as of the end of the period covered by the report[131](index=131&type=chunk) - No material changes were made to the company's internal control over financial reporting during the quarter ended June 30, 2021[132](index=132&type=chunk) [PART II OTHER INFORMATION](index=24&type=section&id=PART%20II%20OTHER%20INFORMATION) [Item 1. Legal Proceedings](index=24&type=section&id=Item%201.%20Legal%20Proceedings) The company faces a new lawsuit seeking at least **$6.0 million** in damages over alleged false representations, which it intends to defend - On June 22, 2021, the company was sued by Lorem Vascular, Pte. Ltd. in the District Court for the District of Delaware[133](index=133&type=chunk) - The lawsuit alleges false representations regarding a UK manufacturing facility sold to Lorem in 2019 and seeks at least **$6,000,000** in damages[133](index=133&type=chunk) - The company believes the claims are without merit, intends to vigorously defend the case, and has not accrued any liability as of June 30, 2021[133](index=133&type=chunk) [Item 1A. Risk Factors](index=24&type=section&id=Item%201A.%20Risk%20Factors) There have been no material changes to the risk factors previously disclosed in the Annual Report on Form 10-K - There have been no material changes to the risk factors included in the company's Annual Report on Form 10-K for the year ended December 31, 2020[134](index=134&type=chunk) [Item 6. Exhibits](index=25&type=section&id=Item%206.%20Exhibits) This section lists all exhibits filed with the Form 10-Q, including officer certifications and XBRL data files - This section lists all exhibits filed with the Form 10-Q, including officer certifications (Exhibits 31.1, 31.2, 32.1) and interactive data files (Exhibits 101 and 104)[137](index=137&type=chunk)

[FORM 10-K Filing Information](index=1&type=section&id=FORM%2010-K) [Filing Details](index=1&type=section&id=Filing%20Details) 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](index=2&type=chunk) - The registrant's name is **PLUS THERAPEUTICS, INC.**, previously known as **Cytori Therapeutics, Inc.**[2](index=2&type=chunk) 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](index=1&type=section&id=Registrant%20Status) 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](index=3&type=chunk) - The registrant has filed all required reports during the preceding **12 months** and has submitted electronically every Interactive Data File[3](index=3&type=chunk) - The registrant is classified as a **Non-Accelerated Filer** and a **Smaller Reporting Company**[3](index=3&type=chunk) [Cautionary Statement Regarding Forward-Looking Statements](index=3&type=section&id=CAUTIONARY%20STATEMENT%20REGARDING%20FORWARD-LOOKING%20STATEMENTS) 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](index=8&type=chunk) - 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](index=9&type=chunk) - 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](index=10&type=chunk) [Risk Factor Summary](index=4&type=section&id=RISK%20FACTOR%20SUMMARY) 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](index=14&type=chunk) - 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](index=14&type=chunk) - The audit report includes an emphasis paragraph regarding substantial doubt about the company's ability to continue as a "**going concern**"[14](index=14&type=chunk) [PART I](index=5&type=section&id=PART%20I) [Item 1. Business](index=5&type=section&id=Item%201.%20Business) **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](index=16&type=chunk) - The company utilizes a **nanoscale drug development platform** and has an established, **GMP-validated R&D** and manufacturing facility in San Antonio, TX[17](index=17&type=chunk) - 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](index=18&type=chunk) [Pipeline](index=5&type=section&id=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](index=19&type=chunk)[24](index=24&type=chunk) - **RNL™** is a patented radiotherapy for **recurrent glioblastoma**, currently in a **U.S. NCI-supported Phase 1 dose-finding clinical trial (ReSPECT™)**[24](index=24&type=chunk)[27](index=27&type=chunk) - **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](index=27&type=chunk)[28](index=28&type=chunk) [Licensing](index=6&type=section&id=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](index=29&type=chunk)[32](index=32&type=chunk) 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](index=33&type=chunk) [Manufacturing](index=7&type=section&id=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](index=34&type=chunk) - The facility enables cost-effective drug substance production and control over the manufacturing process[34](index=34&type=chunk) - 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](index=34&type=chunk) [Competition](index=7&type=section&id=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](index=35&type=chunk) - 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](index=36&type=chunk) - **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](index=35&type=chunk) [Intellectual Property](index=8&type=section&id=Intellectual%20Property) 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