Executive Summary / Key Takeaways

• ORLYNVAH's Pivotal Launch: Iterum Therapeutics is poised for a critical commercial launch of ORLYNVAH (oral sulopenem) around August 20, 2025, targeting the U.S. uncomplicated urinary tract infection (uUTI) market, which has seen no new branded oral treatments in over 25 years despite rising antibiotic resistance.
• Significant Market Opportunity & Differentiation: ORLYNVAH, the first oral penem, addresses a substantial unmet need, particularly for 26 million at-risk uUTI patients. Its efficacy against resistant pathogens and favorable safety profile differentiate it from older, less effective generic alternatives.
• Strategic Commercialization & IP Protection: The company has partnered with EVERSANA for a phased, targeted U.S. launch, supported by a commercial supply agreement with ACS Dobfar. ORLYNVAH benefits from 10 years of market exclusivity (until October 2034) and patent protection extending into 2039.
• Critical Liquidity & Capital Needs: Despite recent capital raises and a deferred $20 million Pfizer payment, Iterum faces a "going concern" warning, necessitating further funding. A crucial shareholder vote on September 10, 2025, for additional share authorization and pre-emption rights waiver is vital for financial flexibility.
• High-Stakes Execution: The investment thesis hinges on successful commercial execution, rapid market penetration, and securing additional capital to sustain operations and fund potential expansion, all while navigating a competitive landscape dominated by larger pharmaceutical players.

A New Dawn for Anti-Infectives: Iterum's Urgent Mission

Iterum Therapeutics plc is on the cusp of a transformative moment, transitioning from a development-focused biotechnology firm to a commercial entity with the imminent launch of ORLYNVAH (oral sulopenem). Incorporated in June 2015, Iterum's journey has been dedicated to addressing the global crisis of multi-drug resistant bacterial infections, a mission underscored by its foundational licensing of sulopenem from Pfizer Inc. in November 2015. This strategic focus has culminated in the FDA approval of ORLYNVAH, positioning the company to disrupt a long-neglected yet expansive market.

The uncomplicated urinary tract infection (uUTI) market in the U.S. is a landscape ripe for innovation. For over 25 years, it has seen no new branded oral treatments, leaving physicians and patients reliant on older therapies. These existing options, some approved as far back as 1953, are increasingly challenged by rising antibiotic resistance rates, which can approach 20% and even exceed 30% for the most widely used products. Compounding this issue are the known safety concerns associated with many current oral treatments, forcing physicians to make difficult choices for their patients. Iterum believes this creates a significant unmet need, particularly for the estimated 26 million "at-risk" patients—elderly women, those with comorbidities like diabetes or heart failure, or a history of recurrent infections—who often have limited or no alternative oral antibacterial treatment options.

The ORLYNVAH Differentiator: A Technological Edge

At the heart of Iterum's investment thesis is ORLYNVAH, a novel oral penem antibiotic. Penems belong to a potent and generally safe class of beta-lactam antibiotics, traditionally delivered intravenously. ORLYNVAH's oral formulation, sulopenem etzadroxil-probenecid, represents a significant technological leap, offering the power of a penem in a convenient oral tablet. This innovation is crucial for enabling treatment in community settings, where the need for effective new agents is most acute.

ORLYNVAH has demonstrated potent in vitro activity against a wide variety of gram-negative, gram-positive, and anaerobic bacteria, including those that encode extended-spectrum beta-lactamase (ESBL) or AmpC-type beta-lactamases, which confer resistance to third-generation cephalosporins. This efficacy against resistant strains is a key tangible benefit, providing a much-needed alternative where older drugs are failing. The REASSURE Phase 3 clinical trial, which completed enrollment in October 2023 and reported positive results in January 2024, confirmed ORLYNVAH's statistical non-inferiority and, importantly, demonstrated statistically significant superiority versus Augmentin in the Augmentin-susceptible population. Furthermore, ORLYNVAH boasts a 6-year shelf life from the date of manufacture, an operational advantage that simplifies distribution and inventory management compared to competitors with shorter expiration timeframes. This technological differentiation, coupled with a favorable safety profile compared to some widely used antibiotics like fluoroquinolones, positions ORLYNVAH to capture value by addressing critical gaps in patient care.

Strategic Commercialization: A Targeted Approach

Following the FDA approval of ORLYNVAH on October 25, 2024, Iterum initially explored strategic transactions to sell or license its sulopenem rights. However, as these discussions did not yield an acceptable outcome, the company pivoted in Q1 2025 to focus on preparing for the direct commercial launch of ORLYNVAH in the U.S. This strategic shift reflects a belief in the product's standalone potential and the urgency to meet patient needs.

To execute this launch, Iterum has forged a partnership with EVERSANA Life Science Services, LLC, an end-to-end commercialization firm. EVERSANA will provide comprehensive services, including sales, commercial operations, marketing, logistics, and medical affairs, while Iterum retains legal, regulatory, and manufacturing responsibilities and will book sales. The company has also brought on Christine Coyne as Chief Commercial Officer, leveraging her 30 years of experience in pharmaceutical and biotech commercialization, including successful antibiotic and antifungal launches. The initial launch phase, expected around August 20, 2025, will be highly targeted, focusing sales resources on 20 specific geographic territories across seven states (NY, NJ, CT, PA, GA, FL, TX). These territories were selected based on high-value physician prescribing patterns, local antibiotic resistance rates, and anticipated market access. This targeted approach aims to reach approximately 2,300 high-value prescribers, primarily primary care physicians, OB/GYNs, and urologists, who collectively write between 1 million and 2 million uUTI prescriptions annually.

Pricing for ORLYNVAH's wholesaler acquisition cost (WAC) is set within the range of $1,400 to $4,700 per course of treatment, aligning with other oral antibiotic launches that have achieved good market access. Iterum also plans to implement patient support programs to help defray out-of-pocket expenses. Operational readiness is further solidified by a commercial manufacturing and supply agreement with ACS Dobfar S.p.A. in Italy, a world-class FDA-approved manufacturer. Current product stock in the U.S. is projected to satisfy commercial requirements into mid-to-late 2026. A key operational focus is "speed to therapy," with a specialty pharmacy selected to streamline prior authorizations and offer various delivery options, ensuring patients receive ORLYNVAH as quickly as possible.

Intellectual Property and Market Protection

Iterum has established a robust intellectual property framework for ORLYNVAH. The FDA has designated ORLYNVAH as a Qualified Infectious Disease Product (QIDP) for uUTIs and other indications. This designation, under the GAIN Act, provides an additional five years of market exclusivity, resulting in a total of 10 years of market exclusivity in the U.S. from the approval date, extending until October 25, 2034.

Beyond market exclusivity, Iterum's U.S. patent portfolio provides protection for ORLYNVAH into 2039, with issued U.S. patents covering both method of use and composition of matter. Four U.S. patents for ORLYNVAH are listed in the FDA's Orange Book. The company also holds a Canadian patent granted in July 2025, along with other foreign patents and numerous pending patent applications globally. This layered intellectual property protection provides a significant runway for Iterum to capture value without immediate generic competition.

Financial Performance and Liquidity: A High-Stakes Transition

Iterum's financial profile reflects its transition from a pure R&D company to a commercial one. For the six months ended June 30, 2025, the company reported a GAAP net loss of $11.4 million, compared to $12.1 million for the same period in 2024. The net loss for the full year 2024 was $24.8 million. Research and development expenses decreased to $1 million in Q2 2025 from $2.1 million in Q2 2024, primarily due to the completion of the REASSURE trial and reduced headcount. Conversely, general and administrative expenses surged to $4.2 million in Q2 2025 from $1.9 million in Q2 2024, driven by pre-commercialization activities. Cost of sales, at $345,000 in Q2 2025, is primarily attributed to the amortization of the intangible asset recognized upon ORLYNVAH's approval.

As of June 30, 2025, Iterum held $13 million in cash and cash equivalents. While management projects this, combined with $2.2 million in ATM proceeds from July 1 to August 1, 2025, will fund operations into 2026, the company has explicitly identified conditions that raise "substantial doubt about its ability to continue as a going concern" for the next 12 months from the 10-Q filing date. This highlights the critical need for successful commercialization and/or additional financing.

Iterum has actively managed its capital structure. In January 2025, it successfully repaid $14.7 million in principal and accrued interest on its Exchangeable Notes. Furthermore, a $20 million regulatory milestone payment to Pfizer , initially due in October 2026, has been deferred to October 25, 2029, with the interest rate increasing from 8% to 10% from October 26, 2026. This deferral provides crucial near-term financial flexibility. To bolster its long-term financial position, Iterum is seeking shareholder approval at its September 10, 2025 Annual General Meeting to authorize an additional 80 million ordinary shares (a 100% increase) and a waiver of pre-emption rights. This move is framed as essential "good housekeeping" to ensure the financial flexibility needed to fund strategic objectives, including the commercial launch, until the company reaches cash flow breakeven. Without the waiver, the company would be limited to more costly and dilutive financing options.

Competitive Landscape and Positioning

Iterum Therapeutics operates in a highly competitive anti-infective market, facing formidable opponents ranging from large, diversified pharmaceutical giants to smaller, specialized biotech firms. Its direct competitors include established players like Pfizer Inc. (PFE), Merck & Co., Inc. (MRK), Johnson & Johnson (JNJ) (via its Janssen division), and AbbVie Inc. (ABBV), all of whom possess significantly greater financial resources, extensive R&D capabilities, and global distribution networks. These larger companies typically exhibit strong revenue growth, high profitability margins, and robust cash flow generation, as evidenced by Pfizer's 2024 current ratio of 1.17 and net profit margin of 0.13, Merck's 2024 current ratio of 1.36 and net profit margin of 0.27, J&J's 2024 current ratio of 1.11 and net profit margin of 0.16, and AbbVie's 2024 net profit margin of 0.08. In contrast, Iterum, with no product revenue to date and a TTM net profit margin of 0.00%, is a clinical-stage company with a more volatile financial profile.

However, Iterum's competitive edge lies in its focused R&D strategy and the unique positioning of ORLYNVAH. While larger competitors offer broad anti-infective portfolios, ORLYNVAH is the first oral penem, addressing a specific and critical unmet need in uUTIs where existing generic therapies (like Nitrofurantoin, approved in 1953, and others from the 1970s-80s) are losing efficacy due to resistance and carry safety concerns. This differentiation allows Iterum to target a niche where it can potentially establish strong market share. The 6-year shelf life of ORLYNVAH also provides an operational advantage over products with shorter expiration dates.

The competitive landscape is evolving, with new entrants like a product approved in April 2024 (yet to launch) and GlaxoSmithKline's (GSK) uUTI product, approved in Q1 2025 and launching in H2 2025. This intensifies the urgency for Iterum's launch. Indirect competitors include vaccine developers (e.g., Moderna (MRNA), BioNTech (BNTX)), generic drug manufacturers (e.g., Teva (TEVA)), and diagnostic firms (e.g., Roche (RHHBY)), which could impact demand for anti-infective treatments. Broader industry trends, such as the increasing role of AI in drug development, could also favor larger, resource-rich competitors by enhancing R&D efficiency, though such impacts are indirect. Iterum's smaller scale and reliance on third-party manufacturers (like ACS Dobfar) for supply, while mitigated by existing agreements, represent vulnerabilities compared to the integrated supply chains of its larger rivals.

Conclusion

Iterum Therapeutics stands at a pivotal juncture, poised to introduce ORLYNVAH into a U.S. uUTI market desperately in need of innovation. The company's journey, marked by persistent R&D and strategic capital raising, has culminated in the FDA approval of a differentiated oral penem antibiotic. ORLYNVAH's unique technological advantages, coupled with a targeted commercialization strategy and robust intellectual property protection, lay a compelling foundation for value creation.

However, the path forward is not without significant challenges. Iterum's "going concern" status underscores the critical need for successful commercial execution and continued access to capital. The upcoming shareholder vote on share authorization and pre-emption rights is paramount for securing the financial flexibility required to sustain and expand its commercial efforts. While competing against pharmaceutical behemoths with vast resources, Iterum's focused approach and ORLYNVAH's distinct clinical profile offer a credible opportunity to address a substantial unmet medical need. Investors should closely monitor the initial commercial launch's traction, the outcome of financing initiatives, and the company's ability to effectively scale operations and manage its liquidity in this high-stakes environment.