Actinium Pharmaceuticals, Inc. annual report, FY2020

Actinium Pharmaceuticals, Inc. — FY2020 Form 10-K

Reporting period: Fiscal year ended December 31, 2020. This is an annual report, not a quarterly filing; the “2020 Q4” metadata does not change the reporting period. The filing was signed March 31, 2021. Actinium is a clinical-stage biopharmaceutical company developing antibody radiation-conjugates (ARCs), with no products approved for sale and no commercial revenue.

Financial performance and liquidity

Metric	2020	2019
Revenue	$0	$0
Research and development expense, net	$16.1 million	$16.6 million
General and administrative expense	$6.3 million	$5.5 million
Operating loss	$22.4 million	$22.1 million
Net loss	$22.2 million	$21.9 million
Basic and diluted loss per share	$1.83	$4.40
Cash used in operating activities	$21.6 million	$21.5 million

R&D spending declined modestly as lower CD33 program costs were mostly offset by higher CD45 costs. G&A rose primarily from professional fees, consultants, investor relations and recruiting. Net loss increased $0.3 million year over year. Operating margins are not meaningful because the company had no revenue.

At year-end, cash and cash equivalents were $63.6 million, versus $9.3 million a year earlier; total assets were $66.4 million, total liabilities $5.1 million and stockholders’ equity $61.3 million. Cash, cash equivalents and restricted cash totaled $64.0 million. Financing activities provided $76.2 million, primarily from equity offerings and share sales; investing activities used $0.3 million. The company reported no off-balance-sheet arrangements. Debt consisted mainly of lease obligations; the $0.4 million note payable outstanding in 2019 was repaid in 2020. Current and long-term lease liabilities totaled approximately $0.7 million.

Actinium raised net proceeds of approximately $29.1 million and $23.0 million from April and June 2020 offerings, respectively, and $21.7 million from its JonesTrading sales agreement through year-end. After year-end, it sold 1.7 million additional shares under that agreement for $14.4 million net. Management expected existing resources to fund planned operations for more than 12 months from the filing date; this is not a guarantee and depends on spending, trial progress and access to further financing. Share issuance creates dilution risk. The company reported an accumulated deficit of $231.0 million.

Business, clinical programs and material developments

Iomab-B / SIERRA: Lead CD45-targeted conditioning candidate in a pivotal Phase 3 randomized trial for patients aged 55 or older with active relapsed or refractory AML, ahead of bone marrow transplant. The planned enrollment is 150; the primary endpoint is durable complete remission at 180 days, with overall survival as a secondary endpoint. Enrollment reached 113 patients (75%) in Q3 2020. In December, the independent DMC recommended continuing to full enrollment after reviewing unblinded data; Actinium did not receive the interim efficacy results. The company expected to complete enrollment and report topline data, which it believed could support a BLA, but the filing provides no definitive completion date or outcome.
Among the first 113 SIERRA patients, company-reported data included BMT for all 49 study-arm patients receiving therapeutic Iomab-B, versus 10 of 57 control-arm patients receiving BMT after remission on salvage therapy. Reported 100-day transplant-related mortality was 4% (2/45) for study-arm transplant recipients versus 20% (2/10) for control-arm transplant recipients. These are interim clinical observations, not final proof of the trial’s primary endpoint; crossover patients were counted as failures for that endpoint.
Iomab-ACT: Lower-dose CD45 ARC development for conditioning before CAR-T/adoptive cell therapy and gene therapy. A Memorial Sloan Kettering collaboration began enrolling a CAR-T study, with proof-of-concept data expected in 2021. A University of California Davis collaboration is studying conditioning in an HIV-related lymphoma gene-therapy trial. In March 2021, Actinium announced preclinical results for an Ac-225 CD45 ARC; this is a post-year-end development and not clinical efficacy evidence.
Actimab-A / CD33: Development emphasizes combinations and targeted conditioning. In a Phase 1 Actimab-A plus CLAG-M study, 10 of 15 patients achieved CR or CRi across dose cohorts; all three patients in the 0.75 μCi/kg cohort achieved CR. No dose-limiting toxicities were reported at that dose, and the study escalated to 1.0 μCi/kg. In the first cohort of the Actimab-A plus venetoclax study, 2 of 3 patients responded, including one CR and one partial response. These small early-stage cohorts require confirmation.
Actimab-MDS: The company planned a Phase 1 dose-finding study in high-risk MDS, potentially followed by a randomized trial that could support a BLA, subject to results and regulatory requirements.
The AWE platform includes more than 140 issued and pending patent applications, according to the filing’s overview; the later intellectual-property disclosure reports 143 issued and pending applications. In January 2021, Actinium announced an Astellas research collaboration for solid-tumor theranostics. No material collaboration revenue amount is clearly provided.

Outlook, risks and other notable items

The company remains dependent on clinical development, particularly the SIERRA trial, and anticipates ongoing losses and substantial R&D spending. Its outlook is conditional: clinical results, regulatory review and financing are uncertain, and the filing gives no revenue, earnings or commercial-launch guidance. Iomab-B’s EU regulatory path may require a partner, which Actinium intended to seek.

Key risks include trial failure or delay, adverse effects, enrollment challenges, regulatory rejection or requests for additional studies, and uncertain reimbursement and market acceptance.
Actinium relies on third parties for clinical trials, drug manufacturing and isotope supply. The Ac-225 supply agreement with the Department of Energy was subject to annual renewal and ran through 2021; interruption or insufficient supply could delay development. The company also identified dependence on a single third-party manufacturer for clinical drug supply.
COVID-19 had not caused a material financial impact or significant clinical-development delay as of the filing, and no sites were then reported as not enrolling because of COVID-19. However, the company warned that renewed restrictions, hospital-resource pressures, supply disruption or capital-market volatility could affect operations and timelines.
Additional risks include potential equity dilution, uncertain patent protection (including expired key lintuzumab antibody patents), and limitations on the use of tax attributes after ownership changes. Federal and state NOL carryforwards were $152.0 million and $81.7 million, respectively; the company maintained a full valuation allowance against deferred tax assets.
The company effected a 1-for-30 reverse stock split in August 2020; reported share and per-share figures were retrospectively adjusted. The auditor issued an unqualified opinion on the financial statements and reported no critical audit matters. Management concluded disclosure controls and internal control over financial reporting were effective; the auditor did not attest to internal controls.

Important facts for investors to verify

Current SIERRA enrollment, final topline results, endpoint analysis and any subsequent FDA or EMA feedback; distinguish final trial outcomes from interim and conference-reported data.
Cash balance, operating cash burn, actual financing raised after March 31, 2021, remaining availability under equity sales agreements and resulting dilution.
Progress and safety findings in Iomab-ACT, Actimab-A combinations and Actimab-MDS, including whether anticipated 2021 milestones were achieved.
Renewal and capacity of Ac-225 supply, diversification of manufacturing sources, and readiness of clinical and potential commercial supply.
Patent status, licensing obligations and any future partner terms, particularly for Iomab-B in Europe and the Astellas collaboration.