Executive Summary / Key Takeaways

• Monopar Therapeutics is a clinical-stage biopharmaceutical company pursuing a dual strategy in rare diseases (Wilson disease with ALXN1840) and oncology (radiopharmaceuticals targeting uPAR with MNPR-101 platform).
• The recent in-licensing of late-stage ALXN1840 provides a potential near-term regulatory catalyst with an NDA submission planned for early 2026, despite prior termination by Alexion based on mechanistic trial data, not safety.
• The proprietary MNPR-101 radiopharmaceutical platform, leveraging a humanized antibody targeting uPAR, is advancing through Phase 1 imaging (MNPR-101-Zr) and therapeutic (MNPR-101-Lu) trials, with preclinical work ongoing for the alpha-emitter conjugate (MNPR-101-Ac).
• As of March 31, 2025, Monopar held $54.60 million in cash, cash equivalents, and investments, which management estimates is sufficient to fund operations at least through December 31, 2026, covering key near-term pipeline milestones.
• Significant future funding will be required beyond the current runway to support later-stage clinical development, potential regulatory approvals, and commercialization efforts, posing a key risk and potential source of dilution.

A Strategic Pivot in Pursuit of Unmet Needs

Monopar Therapeutics Inc. is a clinical-stage biopharmaceutical company strategically positioned at the intersection of rare diseases and oncology. Since its founding in 2014, the company has focused on building a pipeline of drug candidates through a blend of internal research and in-licensing, leveraging its team's extensive experience in drug development and commercialization. This journey has seen the company evolve from early-stage preclinical work to managing multiple clinical programs, notably marked by its initial public offering in December 2019 and subsequent capital raises to fuel its ambitious development goals. The company's overarching strategy is to acquire, develop, and commercialize innovative treatments for patients with unmet medical needs, a goal it pursues by focusing on candidates with existing scientific and clinical data to potentially de-risk further development.

The biopharmaceutical industry is characterized by high R&D costs, lengthy development timelines, and significant regulatory hurdles, creating substantial barriers to entry for smaller players. Large pharmaceutical companies like Bristol-Myers Squibb (BMY), Merck & Co. (MRK), Pfizer Inc. (PFE), and AstraZeneca PLC (AZN) dominate the oncology landscape with vast resources, diversified portfolios, and established market presence. Monopar operates within this competitive environment by targeting specific niches and leveraging differentiated technology, aiming to carve out a unique position. While larger competitors benefit from scale, robust cash flows, and extensive commercial infrastructure, Monopar seeks to differentiate through the precision and potential efficacy of its targeted therapies and its agility in pursuing promising, albeit sometimes de-prioritized, assets from larger firms.

Technological Edge and Pipeline Advancement

Central to Monopar's strategy is its proprietary technology platform, particularly the humanized monoclonal antibody, MNPR-101. This antibody targets the urokinase plasminogen activator receptor (uPAR), a protein highly expressed on several aggressive and deadly cancers, including pancreatic, breast, ovarian, colorectal, and bladder cancers. The strategic intent behind targeting uPAR is to deliver therapeutic or imaging agents directly to cancer cells, potentially increasing efficacy while minimizing exposure and toxicity to healthy tissues.

Monopar is developing MNPR-101 as a versatile platform by conjugating it with different radioisotopes. MNPR-101-Zr, conjugated with zirconium-89, is being evaluated as a radiodiagnostic imaging agent in a first-in-human Phase 1 trial in Australia. Early clinical data has reportedly validated its tumor-targeting ability. For therapeutic applications, MNPR-101-Lu, conjugated with lutetium-177, is in a first-in-human Phase 1a trial in Australia, actively enrolling patients. The company is also advancing MNPR-101-Ac, conjugated with the potent alpha-emitter actinium-225, in late preclinical development. A provisional patent application has been filed covering new radiopharmaceutical compounds and linkers, including a PCTA linker used with Ac-225, which has shown superior binding and yield with MNPR-101 compared to the current industry-leading linker, DOTA. Furthermore, the MNPR-101 antibody has been engineered to be 95% human sequence using licensed technology from XOMA (XOMA), aiming to reduce immunogenicity. These technological efforts represent Monopar's attempt to build a competitive moat through targeted delivery and optimized radioconjugation chemistry.

In a significant strategic move in October 2024, Monopar in-licensed ALXN1840 (tiomolybdate choline) from Alexion, a subsidiary of AstraZeneca. This late-stage, oral drug candidate is for the treatment of Wilson disease, a rare genetic disorder causing toxic copper accumulation. While Alexion terminated the program based on Phase 2 mechanistic trial results and regulatory discussions (not safety), Monopar sees potential in the asset, particularly given the positive outcome of the pivotal Phase 3 trial which met its primary endpoint of copper mobilization. Recent long-term efficacy and safety data presented at EASL 2025 further support its potential use, showing sustained symptom improvements, increased copper mobilization, and favorable safety. This acquisition diversifies Monopar's pipeline beyond oncology and provides a potential near-term regulatory opportunity.

Financial Footing and Future Capital Needs

As a clinical-stage biopharmaceutical company without approved products, Monopar has historically incurred significant losses and negative cash flows. This trend continued in the first quarter of 2025, with a net loss of $2.62 million, compared to $1.64 million in the same period of 2024. Operating expenses totaled $3.22 million for the three months ended March 31, 2025, an increase from $1.72 million in the prior-year period. This rise was primarily driven by increased research and development expenses ($1.64 million vs. $966,000), reflecting higher personnel costs and clinical trial activity for the MNPR-101 program, and increased general and administrative expenses ($1.58 million vs. $757,000), largely due to higher Board compensation and personnel costs.

Despite the operating losses, Monopar's liquidity position saw a substantial improvement following significant financing activities in the fourth quarter of 2024, including public offerings and a private placement, which raised over $55 million. As of March 31, 2025, the company held $39.71 million in cash and cash equivalents and $14.84 million in investments, totaling $54.60 million. This compares favorably to $45.82 million in cash and cash equivalents and $14.40 million in investments as of December 31, 2024. The increase in interest income to $596,845 in Q1 2025 from $82,165 in Q1 2024 directly reflects the larger cash balances.

Net cash used in operating activities increased to $5.66 million in the first quarter of 2025, compared to $1.66 million in the same period of 2024. This increase was primarily attributable to the higher net loss and a $3 million cash payment made in January 2025 related to the ALXN1840 license agreement. Cash flow from financing activities decreased significantly ($115,682 provided in Q1 2025 vs. $3.18 million provided in Q1 2024) as there were no large-scale equity raises in the first quarter of 2025, unlike the at-the-market sales activity in the prior year period.

Management estimates that the current cash position is sufficient to fund planned operations at least through December 31, 2026. This runway is expected to cover the costs associated with assembling and filing the ALXN1840 NDA in early 2026, continuing the MNPR-101-Zr and MNPR-101-Lu clinical trials, advancing the MNPR-101-Ac program, and investing in pipeline expansion. However, achieving regulatory approval and commercializing any product candidate, or advancing the radiopharmaceutical programs through later-stage trials, will require substantial additional long-term funding. The company intends to seek this capital through equity offerings, debt financing, strategic collaborations, or grants, any of which could result in significant dilution to existing shareholders or impose restrictive covenants.

Competitive Dynamics and Strategic Outlook

Monopar faces intense competition across both its rare disease and oncology programs. In Wilson disease, while ALXN1840 has Orphan Drug and Fast Track designations, it will compete with existing standard-of-care treatments and potentially other novel therapies in development. The radiopharmaceutical space is also highly competitive, with numerous companies developing targeted radio-conjugates. Larger competitors possess significant advantages in terms of capital, R&D infrastructure, manufacturing capabilities, and established commercial networks.

Monopar's competitive strategy hinges on the potential differentiation of its assets. For ALXN1840, the focus is on its clinical profile as demonstrated in the Phase 3 trial and its potential as a once-daily oral option for Wilson disease patients, particularly those who may have incomplete or intolerant responses to existing therapies. For the MNPR-101 platform, the differentiation lies in the uPAR target and the specific properties of the humanized antibody and its conjugates, such as the potentially superior binding characteristics with the novel PCTA linker for Ac-225. The company's ability to successfully navigate regulatory pathways, secure manufacturing and supply chains (especially for radioisotopes like Ac-225), and potentially form strategic partnerships will be critical in competing with larger, more established players.

The inclusion of Monopar in the Russell 3000 and Russell 2000 indexes, effective June 27, 2025, may enhance its visibility and liquidity within the market. Furthermore, the recent authorization for an Expanded Access Program (EAP) for MNPR-101-Zr and MNPR-101-Lu in advanced cancers, in collaboration with EDNOC, provides an avenue for patients with urgent unmet needs to potentially access these investigational therapies outside of clinical trials. These developments, while not directly impacting the core clinical trial timelines, signal progress and potential future avenues for patient access and data generation.

Key risks for investors include the inherent uncertainties of clinical trials and regulatory approval, particularly the outcome of the ALXN1840 NDA submission following Alexion's prior decision. The successful development of the MNPR-101 radiopharmaceuticals depends on demonstrating both safety and efficacy in human trials, securing reliable radioisotope supply, and overcoming manufacturing and logistical challenges associated with time-limited radiopharmaceuticals. The company's reliance on third parties for manufacturing and clinical trial execution also presents risks. Ultimately, the need for substantial future funding remains a critical dependency for Monopar's long-term success.

Conclusion

Monopar Therapeutics presents an investment narrative centered on its dual pipeline strategy in Wilson disease and targeted radiopharmaceuticals for oncology. The in-licensed ALXN1840 offers a potential near-term catalyst with an NDA filing planned for early 2026, representing a significant step towards potential commercialization and a test of Monopar's ability to advance an asset through the final regulatory hurdles. Concurrently, the MNPR-101 platform represents a longer-term opportunity in the evolving field of radiopharmaceuticals, leveraging proprietary technology to target aggressive cancers.

While the company's recent financing has provided a cash runway through late 2026, enabling progress on key pipeline milestones, the path to profitability and sustained operations requires substantial additional capital. The success of Monopar's strategy hinges on positive clinical trial outcomes, favorable regulatory decisions, effective management of manufacturing and supply chain complexities, and the ability to secure future funding on acceptable terms. Investors should weigh the potential upside from pipeline advancements and technological differentiation against the significant financial requirements, competitive pressures, and inherent risks associated with clinical-stage biopharmaceutical development.