Spyre Therapeutics, Inc.

Previous wording

We are a clinical stage biotechnology company committed to developing next-generation therapies that elevate the standard in immunology by delivering more complete disease control, greater durability, and a simpler treatment experience for patients. Our pipeline includes extended half-life antibodies targeting α4β7, TL1A, and IL-23 in development as monotherapies and pair-wise combinations.

Current wording

We are a clinical stage biotechnology company committed to developing next-generation therapies that elevate the standard in immunology by delivering more complete disease control, greater durability, and a simpler treatment experience for patients. Our pipeline includes extended half-life antibodies targeting α4β7, TL1A, IL-23, and IL-17A/F (each as defined below), as well as rational combination programs.

Previous wording

Our goal is to develop next-generation therapeutics to redefine the standard of care for the treatment of inflammatory bowel disease (“IBD”) and other immune-mediated diseases, relying on three strategic pillars:

Current wording

Our goal is to develop next-generation therapeutics to elevate the standard of care for the treatment of immune-mediated diseases in the following therapeutic areas:

Previous wording

We are advancing a pipeline of monoclonal antibodies (“mAbs”) for the treatment of IBD and other immune-mediated diseases. The following table (Figure 1) summarizes our pipeline and development strategy, including our SKYLINE Phase 2 platform trial evaluating SPY001, SPY002, SPY003, and pairwise combinations thereof in subjects with moderately to severely active ulcerative colitis (“UC”) and our SKYWAY basket trial evaluating SPY072 in three rheumatic diseases: RA, PsA, and axSpA:

Current wording

We are advancing a pipeline of monoclonal antibodies (“mAbs”) for the treatment of immune-mediated diseases. The following table (Figure 1) summarizes our pipeline and development strategy, including our SKYLINE Phase 2 platform trial evaluating SPY120, SPY130, SPY230, and monotherapy components thereof in subjects with moderately to severely active UC, our SKYLIGHT trial evaluating SPY072 as an add-on to bimekizumab as a proof-of-concept trial for the dual inhibition of anti-TL1A and IL-17A/F, as well as our SPY772 combination program in HS. Additionally, we plan to advance SPY072 monotherapy into pivotal studies for HS in 2027.

Previous wording

•Part A: Open-label assessment of the safety and preliminary efficacy of a single dose level of each investigational monotherapy. Enrollment for Part A has completed, with initial SPY001 and SPY002 Part A topline induction data announced in April 2026 and June 2026, respectively, and with SPY003 topline induction data expected in September 2026.

Current wording

•Part A: Open-label assessment of the safety and preliminary efficacy of a single dose level of each investigational monotherapy. Enrollment for Part A has completed, with initial SPY001, SPY002 and SPY003 Part A topline induction data announced in April 2026, June 2026, and September 2026, respectively.

Previous wording

•Part B: Randomized and placebo-controlled assessment of the safety and efficacy of monotherapies and combinations, designed to provide dose-ranging data on monotherapies, proof-of-concept and contribution of components for combinations, with induction data expected in 2027.

Current wording

•Part B: Randomized and placebo-controlled assessment of the safety and efficacy of monotherapies and combinations, designed to provide dose-ranging data on monotherapies, proof-of-concept and contribution of components for combinations, with induction data expected in Q3 2027. Study is enrolling ahead of schedule, enabling an increased enrollment target.

Previous wording

Topline induction data from Part A of the SKYLINE trial in UC subjects were presented in April 2026 (SPY001) and June 2026 (SPY002). Baseline characteristics were consistent with expectations (Figure 3). SPY001 and SPY002 were well-tolerated with a safety profile consistent with in-class comparators (Figure 4). SPY001 and SPY002 achieved their respective primary endpoints, demonstrating a statistically significant reduction in the RHI score of 9.2 points and 10.7 points, respectively. Rates of key secondary endpoints of clinical remission and endoscopic improvement were clinically meaningful at 40% and 51%, respectively, for SPY001 and 33% and 42%, respectively, for SPY002 (Figure 5). The change in the modified Mayo Score from baseline at Week 12 for both SPY001 and SPY002 was -3.7, reflecting consistency across secondary endpoints. Topline induction data for SPY003 are expected in September 2026.

Current wording

Topline induction data from Part A of the SKYLINE trial in UC subjects were presented in 2026. Baseline characteristics were consistent with expectations (Figure 3). SPY001, SPY002, and SPY003 were well-tolerated with a safety profile consistent with in-class comparators (Figure 4). SPY001, SPY002, and SPY003 achieved their respective primary endpoints, demonstrating a statistically significant reduction in the RHI score of 9.2 points, 10.7 points, and 10.0 points, respectively. Rates of key secondary endpoints of clinical remission and endoscopic improvement were clinically meaningful at 40% and 51%, respectively, for SPY001, 33% and 42%, respectively, for SPY002, and 20% and 30%, respectively, for SPY003 (Figure 5). The change in the modified Mayo Score from baseline at Week 12 for both SPY001 and SPY002 was -3.7, and for SPY003 was -3.5, reflecting consistency across secondary endpoints.

Previous wording

Figure 3. SPY001 and SPY002 baseline demographics from SKYLINE Part A Induction Topline

Current wording

Figure 3. Baseline demographics from SKYLINE Part A Induction Topline

Previous wording

Figure 4. SPY001 and SPY002 safety summary from SKYLINE Part A Induction Topline

Current wording

Figure 4. Safety summary from SKYLINE Part A Induction Topline

Previous wording

Figure 5. SPY001 and SPY002 efficacy summary from SKYLINE Part A Induction Topline

Current wording

Figure 5. Efficacy summary from SKYLINE Part A Induction Topline

Previous wording

In September 2025, we initiated our SKYWAY Phase 2 randomized and placebo-controlled basket trial of SPY072 in subjects with moderately to severely active RA, PsA, or axSpA (Figure 6). The trial consists of three sub-studies, all of which have completed enrollment on or ahead of schedule:

Current wording

In September 2025, we initiated our SKYWAY Phase 2 randomized and placebo-controlled basket trial of SPY072 in subjects with moderately to severely active rheumatic arthritis (“RA”), psoriatic arthritis (“PsA”), or axial spondyloarthritis (“axSpA”). The trial consists of three sub-studies:

Previous wording

•RA sub-study: Double-blind, placebo-controlled safety and efficacy study of two dose levels of SPY072 at Week 12 with open-label follow-up through Week 36. Topline proof-of-concept data are expected in September 2026.

Current wording

•RA sub-study: Double-blind, placebo-controlled safety and efficacy study of two dose levels of SPY072 at Week 12 with open-label follow-up through Week 36. Topline proof-of-concept data were released in August 2026. Both doses of SPY072 demonstrated statistically significant benefits compared to placebo on one or more of the primary (change from baseline in DAS28-CRP), key secondary (ACR20), and exploratory endpoints (ACR50). SPY072 was well tolerated, with a safety profile consistent with the TL1A class. While SPY072 demonstrated clinical activity in RA, the results did not meet the Company’s internal bar to prioritize advancement of SPY072 in RA.

Previous wording

•PsA sub-study: Double-blind, placebo-controlled safety and efficacy study of a single dose level of SPY072 at Week 16 with open-label follow-up through Week 40. Topline proof-of-concept data are expected in the fourth quarter of 2026.

Current wording

•PsA and axSpA sub-studies: Double-blind, placebo-controlled safety and efficacy studies of a single dose level of SPY072 at Week 16 with open-label follow-up through Week 40. In November 2026, we announced that SPY072 was well-tolerated but neither sub-study met its primary endpoint of ACR20 response in PsA or change from baseline in ASDAS in axSpA.

Previous wording

SPY001 is a highly potent, highly selective, and humanized monoclonal immunoglobulin G1 investigational antibody designed to bind selectively to the α4β7 integrin being developed for the treatment of IBD (UC and Crohn’s Disease (“CD”)). The α4β7 integrin is a protein found on the surface of immune cells. This integrin regulates the migration of immune cells to the gut where they contribute to the inflammatory process in IBD. By selectively binding to the α4β7 integrin, SPY001 is designed to prevent the interaction of these immune cells with MAdCAM-1, a molecule expressed on endothelial cells lining the blood vessels in the gut. By blocking the interaction between α4β7 integrin and MAdCAM-1, SPY001 aims to reduce the recruitment of immune cells to the gut, leading to a decrease in inflammation. Since it specifically targets the gut immune system, SPY001 is designed to minimize systemic immunosuppressive effects unrelated to IBD pathology.

Current wording

SPY001 is a highly potent, highly selective, and humanized monoclonal immunoglobulin G1 investigational antibody designed to bind selectively to the α4β7 integrin (“α4β7”) being developed for the treatment of IBD (UC and CD). The α4β7 integrin is a protein found on the surface of immune cells. This integrin regulates the migration of immune cells to the gut where they contribute to the inflammatory process in IBD. By selectively binding to the α4β7 integrin, SPY001 is designed to prevent the interaction of these immune cells with MAdCAM-1, a molecule expressed on endothelial cells lining the blood vessels in the gut. By blocking the interaction between α4β7 integrin and MAdCAM-1, SPY001 aims to reduce the recruitment of immune cells to the gut, leading to a decrease in inflammation. Since it specifically targets the gut immune system, SPY001 is designed to minimize systemic immunosuppressive effects unrelated to IBD pathology.

Previous wording

For our anti-TL1A program, we nominated two highly potent, highly selective, and fully human mAb candidates designed to bind to tumor necrosis factor-like ligand 1A (“TL1A”). SPY002 (formerly SPY002-091) is being developed for the treatment of IBD (UC and CD) and SPY072 (formerly SPY002-072) is being developed for the treatment of RD.

Current wording

For our anti-TL1A program, we nominated two highly potent, highly selective, and fully human mAb candidates designed to bind to tumor necrosis factor-like ligand 1A (“TL1A”). SPY002 (formerly SPY002-091) is being developed for the treatment of IBD (UC and CD) and SPY072 (formerly SPY002-072) is being developed for the treatment of HS, both as a monotherapy and as part of a combination.

Previous wording

TL1A is a protein that plays a role in regulating the immune system and is elevated in gut tissue of individuals with IBD and serum or synovial tissue of individuals with RA, PsA, and axSpA. TL1A interacts with its receptor, death receptor 3 (“DR3”), which is expressed in various immune cells, including T cells and fibroblast-like synoviocytes. This interaction triggers signaling pathways that contribute to inflammation and joint injury in RD, leading to symptomology, such as pain and swelling. SPY002 and SPY072 have been designed to block the interaction between TL1A and DR3, and thereby inhibit the downstream signaling events to dampen the inflammatory response. By neutralizing TL1A, we believe that SPY002 and SPY072 have the potential to modulate the immune response in IBD and rheumatic disease patients, potentially reducing disease activity.

Current wording

TL1A is a protein that plays a role in regulating the immune system and is elevated in tissue of individuals with immune-mediated diseases. TL1A interacts with its receptor, death receptor 3 (“DR3”), which is expressed in various immune cells, triggering signaling pathways that contribute to inflammation. SPY002 and SPY072 have been designed to block the interaction between TL1A and DR3, and thereby inhibit the downstream signaling events to dampen the inflammatory response. By neutralizing TL1A, we believe that SPY002 and SPY072 have the potential to modulate the immune response in patients with immune-mediated diseases, potentially reducing disease activity.

Previous wording

In October 2024, we presented preclinical data, demonstrating in a T-cell transfer model of IBD, that combinations with anti-IL-23 and anti-α4ß7 improved body weight and reduced colonic CD4+ infiltration and IL-17 levels relative to monotherapy. In March and October 2025, we presented additional preclinical data, demonstrating that combinations resulted in superior in vivo biological activity relative to either monotherapy in mouse TNBS model. In addition, combination toxicology studies have been completed with no drug-related adverse findings observed.

Current wording

In October 2024, we presented preclinical data, demonstrating in a T-cell transfer model of IBD, that combinations with anti-IL-23 and anti-α4β7 improved body weight and reduced colonic CD4+ infiltration and IL-17 levels relative to monotherapy. In March and October 2025, we presented additional preclinical data, demonstrating that combinations resulted in superior in vivo biological activity relative to either monotherapy in mouse TNBS model. In addition, combination toxicology studies have been completed with no drug-related adverse findings observed.

Previous wording

In October 2024, we presented preclinical data, demonstrating that anti-IL-23 and anti-TL1A have a synergistic effect on promoting IL-17 secretion from human and mouse cells, and that the combination of anti-IL-23 and anti-TL1A suppressed IL-17 secretion more effectively than either agent alone. In March and October

Current wording

In October 2024, we presented preclinical data, demonstrating that anti-IL-23 and anti-TL1A have a synergistic effect on promoting IL-17 secretion from human and mouse cells, and that the combination of anti-IL-23 and anti-TL1A suppressed IL-17 secretion more effectively than either agent alone. In March and October 2025, we presented additional preclinical data, demonstrating that combinations resulted in superior in vivo biological activity relative to either monotherapy in mouse TNBS model. In addition, combination toxicology studies have been completed with no drug-related adverse findings observed.

Previous wording

On July 12, 2023, December 14, 2023 and June 5, 2024, we exercised our Option available under the Paragon Agreement with respect to the SPY001, SPY002 and SPY003 research programs, respectively. In May 2024, we signed license agreements with Paragon for rights to royalty-bearing, world-wide, exclusive licenses to develop, manufacture, commercialize or otherwise exploit certain antibodies and products targeting ɑ4β7 integrin (SPY001 program) (the “SPY001 License Agreement”) and TL1A (SPY002 and SPY072 programs) (the “SPY002 and SPY072 License Agreement”) and, in October 2024, we signed a license agreement for rights to a royalty-bearing, world-wide, exclusive license to develop, manufacture, commercialize or otherwise exploit certain antibodies and products targeting IL-23 (SPY003 program) (the “SPY003 License Agreement” and, together with the SPY001 License Agreement and the SPY002 and SPY072 License Agreement, the “License Agreements”) in the field of IBD. The SPY003 License Agreement was subsequently amended and restated in February 2025 and further amended in May 2026 to expand the definition of “Field” to encompass all therapeutic, prophylactic, palliative and diagnostic uses for SPY003, subject to certain restrictions. The Option with respect to one additional program remains unexercised under the Paragon Agreement.

Current wording

On July 12, 2023, December 14, 2023 and June 5, 2024, we exercised our Option available under the Paragon Agreement with respect to the SPY001, SPY002 and SPY072, and SPY003 research programs, respectively. In May 2024, we signed license agreements with Paragon for rights to royalty-bearing, world-wide, exclusive licenses to develop, manufacture, commercialize or otherwise exploit certain antibodies and products targeting α4β7 integrin (SPY001 program) (the “SPY001 License Agreement”) and TL1A (SPY002 and SPY072 programs) (the “SPY002 and SPY072 License Agreement”) and, in October 2024, we signed a license agreement for rights to a royalty-bearing, world-wide, exclusive license to develop, manufacture, commercialize or otherwise exploit certain antibodies and products targeting IL-23 (SPY003 program) (the “SPY003 License Agreement” and, together with the SPY001 License Agreement and the SPY002 and SPY072 License Agreement, the “License Agreements”) in the field of IBD. The SPY003 License Agreement was subsequently amended and restated in February 2025 and further amended in May 2026 to expand the definition of “Field” to encompass all therapeutic, prophylactic, palliative and diagnostic uses for SPY003, subject to certain restrictions. The Option with respect to one additional program remains unexercised under the Paragon Agreement.

Previous wording

We define our critical accounting policies as those accounting principles generally accepted in the United States that require us to make subjective estimates and judgments about matters that are uncertain and are likely to have a material impact on our financial condition and results of operations, as well as the specific manner in which we apply those principles. There have been no significant changes to our critical accounting policies and estimates as compared to the critical accounting policies and estimates disclosed in “Management’s Discussion and Analysis of Financial Condition and Operations” included in our Annual Report, except as disclosed below:

Current wording

We define our critical accounting policies as those accounting principles generally accepted in the United States that require us to make subjective estimates and judgments about matters that are uncertain and are likely to have a material impact on our financial condition and results of operations, as well as the specific manner in which we apply those principles. There have been no significant changes to our critical accounting policies and estimates as compared to the critical accounting policies and estimates disclosed in “Management’s Discussion and Analysis of Financial Condition and Results of Operations” included in our Annual Report, except as disclosed below:

Previous wording

As of June 30, 2026, Contingent Value Rights are no longer a critical accounting policy or estimate. We determined that our future payment obligations under the contingent value rights agreement (the "CVR Agreement") we entered into with Equiniti Trust Company LLC (f/k/a American Stock Transfer & Trust Company LLC) as rights agent in connection with the Asset Acquisition no longer qualify as derivatives under ASC 815, Derivatives and Hedging, as all contingencies have been resolved. Accordingly, we have measured the fair value of our CVR liability by discounting the estimated future payments to be made under the CVR Agreement using our weighted average cost of capital. The estimated value of the CVR consideration is based upon available information and certain assumptions which our management believes are reasonable under the circumstances. The ultimate payout under the CVRs may differ materially from the assumptions used in determining the fair value of the CVR consideration.

Current wording

As of June 30, 2026, Contingent Value Rights (“CVRs”) are no longer a critical accounting policy or estimate. We determined that remaining significant contingencies regarding our future payment obligations under the contingent value rights agreement (the “CVR Agreement”) we entered into with Equiniti Trust Company LLC (f/k/a American Stock Transfer & Trust Company LLC) as rights agent in connection with the Asset Acquisition have been resolved. Accordingly, we have measured the fair value of our CVR liability by discounting the estimated future payments to be made under the CVR Agreement using our weighted average cost of capital. The estimated value of the CVR consideration is based upon available information and certain assumptions which our management believes are reasonable under the circumstances. The ultimate payout under the CVRs may differ materially from the assumptions used in determining the fair value of the CVR consideration.

Previous wording

Research and Development Expenses. Research and development expenses increased by $25.4 million, or 63%, to $65.5 million for the three months ended June 30, 2026, from $40.1 million for the three months ended June 30, 2025. The increase was primarily driven by higher manufacturing expenses, clinical trial expenses, and compensation costs partially offset by lower early-stage research and development costs.

Current wording

Research and Development Expenses. Research and development expenses increased by $43.9 million, or 97%, to $89.2 million for the three months ended September 30, 2026, from $45.2 million for the three months ended September 30, 2025. The increase was primarily driven by higher manufacturing expenses, clinical trial expenses, and compensation costs partially offset by a decrease in licensing fees.

Previous wording

External research and development expenses include costs associated with third parties contracted to conduct research and development activities on our behalf, including through Paragon, contract research organizations (“CROs”), contract manufacturing organizations (“CMOs”), and third-party laboratories. For the three months ended June 30, 2026 and 2025, external research and development costs accounted for $49.9 million and $30.4 million, respectively. Preclinical expenses decreased primarily due to a reduction in early-stage research and development activities given our pipeline's advancement. IBD and Rheumatic diseases expenses increased primarily due to an increase in manufacturing costs and clinical development activities related to ongoing or planned clinical trials.

Current wording

External research and development expenses include costs associated with third parties contracted to conduct research and development activities on our behalf including through contract research organizations (“CROs”), contract manufacturing organizations (“CMOs”), and third-party laboratories. For the three months ended September 30, 2026 and 2025, external research and development costs accounted for $73.2 million and $34.3 million, respectively. Preclinical expenses increased primarily due to SPY007 pre-clinical development costs. Gastroenterology and Rheumatology program expenses increased primarily due to an increase in manufacturing costs and clinical development activities related to ongoing or planned clinical trials. Dermatology program expenses increased primarily due to the initiation of clinical development activities.

Previous wording

Internal research and development expenses include compensation and related costs associated with our research and development employees. For the six months ended June 30, 2026 and 2025, internal research and development costs accounted for $29.8 million and $17.9 million, respectively. The increase was primarily driven by an increase in research and development headcount.

Current wording

Internal research and development expenses include compensation and related costs associated with our research and development employees. For the three months ended September 30, 2026 and 2025, internal research and development costs accounted for $16.0 million and $10.9 million, respectively. The increase was primarily driven by an increase in research and development headcount.

Previous wording

General and Administrative Expenses. General and administrative expenses increased by $4.3 million, or 37%, to $16.1 million for the three months ended June 30, 2026, from $11.8 million for the three months ended June 30, 2025. The increase was primarily attributable to an increase in compensation costs due to an increase in general and administrative headcount.

Current wording

General and Administrative Expenses. General and administrative expenses increased by $4.9 million, or 42%, to $16.6 million for the three months ended September 30, 2026, from $11.6 million for the three months ended September 30, 2025. The increase was primarily attributable to an increase in general and administrative headcount as well as professional services costs.

Previous wording

Interest Income. Interest income was $10.1 million and $5.9 million for the three months ended June 30, 2026 and 2025, respectively. The increase was primarily due to higher investment balances.

Current wording

Interest Income. Interest income was $10.6 million and $5.4 million for the three months ended September 30, 2026 and 2025, respectively. The increase was primarily due to higher investment balances.

Previous wording

The following table summarizes our results of operations for the six months ended June 30, 2026 and 2025, together with the changes in those items in dollars and as a percentage:

Current wording

The following table summarizes our results of operations for the nine months ended September 30, 2026 and 2025, together with the changes in those items in dollars and as a percentage:

Previous wording

Research and Development Expenses. Research and development expenses increased by $44.1 million, or 54%, to $125.9 million for the six months ended June 30, 2026, from $81.8 million for the six months ended June 30, 2025. The increase was primarily driven by higher manufacturing expenses, clinical trial expenses, and compensation costs, partially offset by lower early-stage research and development.

Current wording

Research and Development Expenses. Research and development expenses increased by $88.1 million, or 69%, to $215.1 million for the nine months ended September 30, 2026, from $127.0 million for the nine months ended September 30, 2025. The increase was primarily driven by higher manufacturing expenses, clinical trial expenses, and compensation costs, partially offset by lower early-stage research and development.

Previous wording

External research and development expenses include costs associated with third parties contracted to conduct research and development activities on our behalf, including through Paragon, CROs, CMOs, and third- party laboratories. For the six months ended June 30, 2026 and 2025, external research and development costs accounted for $96.1 million and $63.9 million, respectively. Preclinical expenses decreased primarily due to a reduction in early-stage research and development activities given our pipeline's advancement. IBD and Rheumatic diseases expenses increased primarily due to an increase in manufacturing costs and clinical development activities related to ongoing or planned clinical trials.

Current wording

External research and development expenses include costs associated with third parties contracted to conduct research and development activities on our behalf including through CROs, CMOs, and third-party laboratories. For the nine months ended September 30, 2026 and 2025, external research and development costs accounted for $169.3 million and $98.2 million, respectively. Preclinical expenses decreased primarily due to a reduction in early-stage research and development activities given our pipeline's advancement, partially offset by an increase in SPY007 preclinical development costs. Gastroenterology and Rheumatology program expenses increased primarily due to an increase in manufacturing costs and clinical development activities related to ongoing or planned clinical trials. Dermatology program expenses increased primarily due to the initiation of clinical development activities.

Previous wording

Internal research and development expenses include compensation and related costs associated with our research and development employees. For the three months ended June 30, 2026 and 2025, internal research and development costs accounted for $15.6 million and $9.8 million, respectively. The increase was primarily driven by an increase in compensation costs due to an increase in research and development headcount.

Current wording

Internal research and development expenses include compensation and related costs associated with our research and development employees. For the nine months ended September 30, 2026 and 2025, internal research and development costs accounted for $45.7 million and $28.8 million, respectively. The increase was primarily driven by an increase in research and development headcount.

Previous wording

General and Administrative Expenses. General and administrative expenses increased by $7.6 million, or 32%, to $31.4 million for the six months ended June 30, 2026, from $23.7 million for the six months ended June 30, 2025. The increase was primarily attributable to an increase in compensation costs due to an increase in general and administrative headcount.

Current wording

General and Administrative Expenses. General and administrative expenses increased by $12.5 million, or 35%, to $47.9 million for the nine months ended September 30, 2026, from $35.4 million for the nine months ended September 30, 2025. The increase was primarily attributable to an increase in general and administrative headcount as well as professional services costs.

Previous wording

Gain on Sale of In-Process Research and Development Asset. During the six months ended June 30, 2026 and 2025, the Company recognized gains of $70.0 million and $10.0 million, respectively, related to milestone payments earned in connection with the 2023 sale of the global rights to the legacy Aeglea asset pegzilarginase to Immedica. The 2026 gain was triggered by the regulatory approval of pegzilarginase in the United States and the sale of the related PRV, while the 2025 gain was triggered by a favorable reimbursement decision for pegzilarginase in Europe.

Current wording

Gain on Sale of In-Process Research and Development Asset. During the nine months ended September 30, 2026 and 2025, the Company recognized gains of $70.0 million and $10.0 million, respectively, related to milestone payments earned in connection with the 2023 sale of the global rights to the legacy Aeglea Biotherapeutics, Inc. asset pegzilarginase to Immedica.

Previous wording

Interest Income. Interest income was $17.0 million and $12.4 million for the six months ended June 30, 2026 and 2025, respectively. The increase was primarily due to higher investment balances.

Current wording

Interest Income. Interest income was $27.7 million and $17.7 million for the nine months ended September 30, 2026 and 2025, respectively. The increase was primarily due to higher investment balances.

Previous wording

Since our inception and through June 30, 2026, we have funded our operations by raising an aggregate of approximately $2.1 billion of gross proceeds from the sale and issuance of convertible preferred stock and common stock, pre-funded warrants, the collection of grant proceeds, and the licensing of our product rights for commercialization of pegzilarginase in Europe and certain countries in the Middle East. As of June 30, 2026, we had an accumulated deficit of $1.2 billion. In April 2026, we raised an additional approximately $435.2 million in net proceeds from a public underwritten offering of our common stock.

Current wording

Since our inception and through September 30, 2026, we have funded our operations by raising an aggregate of approximately $2.2 billion of gross proceeds from the sale and issuance of convertible preferred stock and common stock, pre-funded warrants, the collection of grant proceeds, and the licensing of our product rights for commercialization of pegzilarginase in Europe and certain countries in the Middle East. As of September 30, 2026, we had an accumulated deficit of $1.3 billion.

Previous wording

On September 6, 2024, the Company entered into a sales agreement (the “2024 Sales Agreement”) with TD Securities (USA) LLC as its agent, pursuant to which the Company may issue and sell up to $200.0 million of shares of common stock under an at-the-market (“ATM”) offering program. During the year ended December 31, 2025, we sold an aggregate of 445,668 shares of common stock under the ATM offering program pursuant to the 2024 Sales Agreement resulting in net proceeds of $14.8 million. During the six months ended June 30, 2026, the Company sold an aggregate of 296,396 shares of common stock under the ATM offering program pursuant to the 2024 Sales Agreement resulting in net proceeds of $9.7 million. The 2024 Sales Agreement was terminated on June 26, 2026 and the Company concurrently entered into a new sales agreement (the “2026 Sales Agreement”) with TD Securities (USA) LLC as its agent, pursuant to which the Company may issue and sell up to $500.0 million of shares of common stock under an ATM offering program. During the three months ended June 30, 2026, the Company did not sell any shares under the ATM offering program pursuant to the 2026 Sales Agreement. As of June 30, 2026, $500.0 million remained available for sale under the 2026 Sales Agreement.

Current wording

On September 6, 2024, the Company entered into a sales agreement (the “2024 Sales Agreement”) with TD Securities (USA) LLC as its agent, pursuant to which the Company may issue and sell up to $200.0 million of shares of common stock under an at-the-market (“ATM”) offering program. During the year ended December 31, 2025, we sold an aggregate of 445,668 shares of common stock under the ATM offering program pursuant to the 2024 Sales Agreement resulting in net proceeds of $14.8 million. During the three and nine months ended September 30, 2026, the Company sold an aggregate of nil and 296,396 shares of common stock, respectively, under the ATM offering program pursuant to the 2024 Sales Agreement resulting in net proceeds of nil and $9.7 million, respectively. The 2024 Sales Agreement was terminated on June 26, 2026 and the Company concurrently entered into a new sales agreement (the “2026 Sales Agreement”) with TD Securities (USA) LLC as its agent, pursuant to which the Company may issue and sell up to $500.0 million of shares of common stock under an ATM offering program. During the three and nine months ended September 30, 2026, the Company sold 327,391 shares under the ATM offering program pursuant to the 2026 Sales Agreement, resulting in net proceeds of $29.5 million. Subsequent to September 30, 2026, and through November 3, 2026, the Company sold 200,111 shares under the ATM offering program pursuant to the 2026 Sales Agreement, resulting in net proceeds of $18.0 million.

Previous wording

Cash used in operating activities for the six months ended June 30, 2026 was $127.2 million and primarily reflected a net loss of $105.2 million adjusted for a $70.0 million non-operating gain on sale of in-process research and development, a $8.8 million decrease in net operating assets and liabilities driven by timing of payments to vendors, a $4.5 million in net accretion of discount on marketable securities, net of interest proceeds from maturities of zero coupon U.S. Treasury Bills, partially offset by non-cash expenses of $34.9 million due to an increase in the fair value of the CVR liability, and $26.3 million for share-based compensation expense.

Current wording

Cash used in operating activities for the nine months ended September 30, 2025 was $124.7 million and primarily reflected a net loss of $92.7 million, adjusted for a $10.0 million gain on sale of in-process research and development, a $42.2 million decrease in the fair value of the CVR liability, $3.9 million of net adjustments related to our marketable securities, and a $3.7 million net cash outflow from changes in operating assets and liabilities, partially offset by non-cash share-based compensation expense of $27.8 million.

Previous wording

Cash used in investing activities for the six months ended June 30, 2026 was $241.3 million and primarily consisted of $528.5 million in purchases of marketable securities, partially offset by $217.2 million in maturities and sales of marketable securities and $70.0 million in proceeds from the sale of an in-process research & development asset.

Current wording

Cash used in investing activities for the nine months ended September 30, 2026 was $245.1 million and primarily consisted of $666.8 million in purchases of marketable securities, partially offset by $351.7 million in maturities and sales of marketable securities and $70.0 million in proceeds from the sale of a legacy in-process research and development asset.

Previous wording

Cash provided by investing activities for the six months ended June 30, 2025 was $78.9 million and primarily consisted of $178.2 million in maturities and sales of marketable securities, $7.0 million in proceeds from the sale of an in-process research & development asset, partially offset by $106.3 million in purchases of marketable securities.

Current wording

Cash provided by investing activities for the nine months ended September 30, 2025 was$103.9 million and primarily consisted of$277.4 million in maturities and sales of marketable securities and$7.0 millionin proceeds from the sale of an in-process research and development asset, partially offset by$180.5 million inpurchases of marketable securities.

Previous wording

Cash provided by financing activities for the six months ended June 30, 2026 was $444.9 million, which primarily consisted of $435.2 million and $9.8 million net proceeds from the issuance of common stock in connection with the April 2026 follow-on offering and ATM offering program, respectively, and $23.3 million proceeds from stock option exercises and sales of common stock under our ESPP, partially offset by a $22.9 million payment to CVR holders.

Current wording

Cash provided by financing activities for the nine months ended September 30, 2026 was $446.9 million, which primarily consisted of $435.2 million and $39.3 million net proceeds from the issuance of common stock in connection with the April 2026 Offering and under our at-the-market offering programs, respectively, and $28.8 million proceeds from stock option exercises and sales of common stock under our ESPP, partially offset by a $55.7 million payment to CVR holders.

Previous wording

Through the Asset Acquisition, we received the Option to license certain intellectual property rights related to certain research programs. The exercise of the Option allows for us to enter into an exclusive license agreement with Paragon for the respective research program. Thus far we have exercised the Option and entered into license agreements with respect to SPY001, SPY002, SPY072 and SPY003. Under the terms of each License Agreement, we are obligated to pay Paragon up to $22.0 million based on specific development, regulatory and clinical milestones for the first product under each agreement. As of June 30, 2026, we have incurred a total of $21.0 million of milestone fees out of a total maximum of $66.0 million in potential milestone fees across all License Agreements. As of June 30, 2026, no achieved milestone fees are outstanding and payable. With respect to the SPY002 and SPY072 License Agreement only, on a product-by-product basis, we are obligated to pay sublicensing fees of up to approximately $20.0 million upon the achievement of mostly commercial milestones. As of June 30, 2026, we have incurred $2.6 million of sublicensing fees of which none is outstanding and payable.

Current wording

Through the Asset Acquisition, we received the Option to license certain intellectual property rights related to certain research programs. The exercise of the Option allows for us to enter into an exclusive license agreement with Paragon for the respective research program. Thus far we have exercised the Option and entered into license agreements with respect to SPY001, SPY002 and SPY072, and SPY003. Under the terms of each License Agreement, we are obligated to pay Paragon up to $22.0 million based on specific development, regulatory and clinical milestones for the first product under each agreement. As of September 30, 2026, we have incurred a total of $21.0 million of milestone fees out of a total maximum of $66.0 million in potential milestone fees across all License Agreements. As of September 30, 2026, no achieved milestone fees are outstanding and payable. With respect to the SPY002 and SPY072 License Agreement only, on a product-by-product basis, we are obligated to pay sublicensing fees of up to approximately $20.0 million upon the achievement of mostly commercial milestones. As of September 30, 2026, we have incurred $2.7 million of sublicensing fees of which $0.1 million is outstanding and payable.

Previous wording

There were no recent adopted accounting pronouncements that have had a material effect on our financial position or results of operations.

Current wording

There were no recently adopted accounting pronouncements that have had a material effect on our financial position or results of operations.