Inozyme Pharma is a clinical-stage biopharmaceutical company dedicated to developing innovative therapies for rare diseases that affect bone health and blood vessel function. The company's expertise lies in the PPi-Adenosine Pathway, where the ENPP1 enzyme plays a crucial role in regulating mineralization and intimal proliferation. Disruptions in this pathway can lead to severe musculoskeletal, cardiovascular, and neurological conditions, including ENPP1 Deficiency, ABCC6 Deficiency, calciphylaxis, and ossification of the posterior longitudinal ligament (OPLL).

Inozyme was founded in 2017 and has since made significant strides in advancing its lead product candidate, INZ-701, an ENPP1 Fc fusion protein enzyme replacement therapy (ERT) designed to address deficiencies in PPi and adenosine. The company has established a robust clinical pipeline, with INZ-701 currently in development for the treatment of ENPP1 Deficiency, ABCC6 Deficiency, and calciphylaxis. In the same year of its founding, Inozyme entered into a crucial license agreement with Yale University to obtain intellectual property rights related to ectonucleotide pyrophosphatase/phosphodiesterase enzymes, which form the foundation of the INZ-701 development program. This agreement has required Inozyme to make various upfront, milestone, and royalty payments to Yale over the years.

The company's journey gained momentum in 2020 when it successfully completed an initial public offering, raising $149.6 million in funding. This significant capital infusion provided Inozyme with the necessary resources to advance INZ-701 into clinical development for ENPP1 Deficiency and ABCC6 Deficiency.

Despite facing initial challenges in navigating the regulatory landscape and obtaining necessary approvals for clinical trials, Inozyme achieved a major milestone in 2021 by dosing the first patient in its Phase 1/2 clinical trial of INZ-701 in adult patients with ENPP1 Deficiency. The company's perseverance paid off in 2022 and 2023 when it reported positive topline data from this trial, demonstrating that INZ-701 was generally well-tolerated and significantly increased plasma PPi levels in patients. These encouraging results validated Inozyme's approach and supported the continued development of INZ-701.

Disease Overview

ENPP1 Deficiency is a rare and progressive disease that affects the vasculature, soft tissues, and skeleton. Individuals with this condition often present in utero or during infancy with generalized arterial calcification of infancy (GACI Type 1), and approximately 50% of these infants do not survive beyond six months. Children with ENPP1 Deficiency typically develop rickets, specifically autosomal-recessive hypophosphatemic rickets type 2 (ARHR2), while adolescents and adults may develop osteomalacia, or softened bones. ARHR2 and osteomalacia can cause pain and difficulty with movement, and patients may also experience hearing loss, calcification in arteries and joints, and heart problems. Currently, there are no approved therapies for ENPP1 Deficiency.

ABCC6 Deficiency is another rare and debilitating condition that affects the vasculature and soft tissues. Infants with ABCC6 Deficiency are diagnosed with generalized arterial calcification of infancy (GACI Type 2), which is similar to GACI Type 1. Pediatric patients who survive beyond the first year of life may develop neurological disease, including strokes, and cardiovascular diseases due to ongoing vascular calcification and stenosis. In older individuals, ABCC6 Deficiency manifests as pseudoxanthoma elasticum (PXE), characterized by abnormal mineralization in blood vessels and soft tissues, affecting the skin, visual function, and vascular system. There are currently no approved therapies for ABCC6 Deficiency.

Calciphylaxis, also known as calcific uremic arteriolopathy (CUA), is a rare disorder with a high mortality rate that predominantly affects patients with end-stage kidney disease (ESKD). The disease is associated with low levels of inorganic pyrophosphate (PPi) and is characterized by pathologic mineralization and intimal proliferation of the vasculature in the skin and fatty tissue, leading to poor blood flow, blood clots, painful skin ulcers, serious infections, and often death. Patients with calciphylaxis have a reported one-year survival rate of approximately 50%, and there are currently no approved therapies for this condition.

Lead Candidate: INZ-701

Inozyme's lead candidate, INZ-701, is designed to address the underlying deficiencies in PPi and adenosine that drive the pathological processes in these rare diseases. In preclinical studies, INZ-701 has demonstrated the potential to prevent pathologic mineralization and intimal proliferation, which can significantly impact morbidity and mortality in these devastating disorders.

The company's clinical development strategy for INZ-701 is comprehensive, with ongoing and planned trials in ENPP1 Deficiency, ABCC6 Deficiency, and calciphylaxis. In the ENPP1 Deficiency program, Inozyme is conducting a Phase 1/2 trial in adults, a Phase 1b trial in infants, and a pivotal Phase 3 trial in pediatric patients. For ABCC6 Deficiency, the company recently reported positive topline data from a Phase 1/2 trial in adults and is preparing to initiate a pivotal trial in pediatric patients, subject to regulatory review and sufficient funding. Additionally, Inozyme has initiated a Phase 1 trial of INZ-701 in patients with end-stage kidney disease (ESKD) receiving hemodialysis, with the goal of addressing the unmet need in calciphylaxis.

Financials

In the first quarter of 2024, Inozyme reported a net loss of $23.3 million, or $0.38 per share, compared to a net loss of $17.4 million, or $0.40 per share, in the prior-year period. Research and development expenses increased to $19.1 million, up from $11.9 million in the first quarter of 2023, reflecting the company's ongoing investment in its clinical programs. General and administrative expenses were $5.2 million, down from $6.5 million in the prior-year quarter.

For the second quarter of 2024, Inozyme reported a net loss of $27.0 million, or $0.44 per share, compared to a net loss of $15.6 million, or $0.35 per share, in the same period of the previous year. Research and development expenses increased to $21.8 million, up from $11.7 million in the second quarter of 2023, while general and administrative expenses were $5.9 million, up from $4.7 million in the prior-year quarter.

In the third quarter of 2024, the company reported a net loss of $24.6 million, or $0.39 per share, compared to a net loss of $16.6 million, or $0.29 per share, in the same period of 2023. Research and development expenses increased to $19.9 million, up from $13.3 million in the third quarter of 2023, while general and administrative expenses were $5.0 million, up from $4.7 million in the prior-year quarter.

For the most recent fiscal year (2023), Inozyme reported no revenue and a net loss of $71,169,000. The company's operating cash flow (OCF) for 2023 was negative $70,675,000, and its free cash flow (FCF) was negative $70,973,000. In the most recent quarter (Q3 2024), the company again reported no revenue, with a net loss of $24,570,000. The OCF for Q3 2024 was negative $24,528,000, and the FCF was negative $24,541,000.

As Inozyme is still in the clinical stage and not yet generating revenue, there is no year-over-year growth data available. The company operates primarily in the United States.

Liquidity

Inozyme's financial position appears strong, with $131.6 million in cash, cash equivalents, and short-term investments as of September 30, 2024. The company's management believes this will enable it to fund its cash flow requirements into the fourth quarter of 2025, providing a solid runway to advance its clinical programs.

The company's liquidity metrics show a debt-to-equity ratio of 0.5632, indicating a moderate level of leverage. Inozyme has $24,570,000 in cash and cash equivalents, along with $107,030,000 in short-term investments. The company also has a $70 million loan agreement with K2 HealthVentures LLC, of which $45 million is currently outstanding. An additional $25 million remains available, subject to certain conditions.

Inozyme's current ratio and quick ratio are both 7.683, suggesting a strong ability to meet short-term obligations. These ratios are identical due to the nature of the company's assets, which are primarily liquid.

Clinical Development Progress

The company's clinical development progress has been marked by several key milestones. In the ENPP1 Deficiency program, Inozyme announced positive topline data from its Phase 1/2 trial in adults, indicating favorable safety, immunogenicity, and clinical outcomes, which were maintained through 48 weeks. The company also plans to initiate a pivotal trial in pediatric patients with ENPP1 Deficiency in the third quarter of 2024.

In the ABCC6 Deficiency program, Inozyme reported positive topline data from its Phase 1/2 trial in adults, demonstrating clinical improvements in vascular pathology, visual function, and patient-reported outcomes. The FDA has granted Fast Track designation to INZ-701 for the treatment of ABCC6 Deficiency, recognizing the potential to address the significant unmet need in this disease. The company plans to initiate a pivotal trial in pediatric patients with ABCC6 Deficiency in the first quarter of 2025, subject to regulatory review and sufficient funding.

Regarding the calciphylaxis program, Inozyme has initiated a Phase 1 trial of INZ-701 in patients with end-stage kidney disease (ESKD) receiving hemodialysis. The company expects to report interim data from this trial in the fourth quarter of 2024, which could provide further validation of INZ-701's potential to address the underlying deficiencies in this devastating condition.

Industry Trends

The global biotechnology market, in which Inozyme operates, is experiencing significant growth. It is expected to grow at a compound annual growth rate (CAGR) of 11.8% and reach $4.25 trillion by 2033. The U.S. market, which is Inozyme's primary focus, is projected to grow even faster, with an 11.90% CAGR, reaching $763.82 billion by 2033. This robust industry growth provides a favorable backdrop for Inozyme's development efforts in rare diseases.

Conclusion

Despite the challenges inherent in developing therapies for rare diseases, Inozyme has demonstrated a steadfast commitment to addressing the significant unmet needs of patients affected by ENPP1 Deficiency, ABCC6 Deficiency, and calciphylaxis. The company's innovative approach, centered on the PPi-Adenosine Pathway, has the potential to transform the lives of these patients and their families.

Inozyme's comprehensive clinical development strategy, coupled with its strong financial position, positions the company well to continue advancing its innovative therapies and addressing the significant unmet needs of patients affected by rare diseases of the PPi-Adenosine Pathway. As the company progresses through its clinical trials and regulatory interactions, investors and the broader rare disease community will be closely following Inozyme's journey to bring transformative treatments to those in urgent need.