What changed in this filing

/stocks — the workspaceLOADING

Item 1. Business

2026-03-02 compared with 2025-03-03 · 479 added, 638 removed, 825 unchanged (58% of the section changed)

We are a clinical stage biotechnology company advancing novel biologics with the potential for differentiated efficacy and dosing in the largest inflammatory and immunology (“I&I”) markets, including for the treatment of atopic dermatitis (“AD”), asthma, eosinophilic esophagitis (“EoE”), chronic obstructive pulmonary disease (“COPD”), and other I&I indications.

We are a clinical stage biotechnology company advancing optimized, novel biologics with the potential for differentiated efficacy and dosing in the largest inflammatory and immunology (“I&I”) markets, including for the treatment of atopic dermatitis (“AD”), asthma, eosinophilic esophagitis (“EoE”), chronic obstructive pulmonary disease (“COPD”), and other I&I indications.

Our antibody programs are designed to overcome limitations of existing therapies by targeting well-established mechanisms of action and incorporating advanced antibody engineering to optimize half-life and other properties.

Our pipeline comprises four antibody programs being developed initially for the treatment of I&I indications as monotherapies and combinations.

Our most advanced programs are APG777, APG990, APG333, and APG808.

Our pipeline comprises multiple antibody programs being developed initially for the treatment of I&I indications as monotherapies and combinations, including zumilokibart (APG777), APG279 (zumilokibart + APG990), APG273 (zumilokibart + APG333), and APG808 (each, a “program” or “product candidate”).

With four validated targets in our portfolio, we are seeking to achieve best-in-class efficacy and dosing through monotherapies and combinations of our novel antibodies.

Based on a broad pipeline and depth of expertise, we believe we can deliver value and meaningful benefit to patients underserved by today’s standard of care.

Our programs incorporate advanced antibody engineering to optimize half-life and other properties designed to overcome limitations of existing therapies.

We believe each of our programs has potential for broad application across multiple I&I indications, including in combination.

In March 2024, we announced positive interim safety, pharmacokinetic (“PK”) and pharmacodynamic (“PD”) data from our Phase 1 trial of APG777 in healthy volunteers and in May 2024, we initiated a Phase 2 trial of APG777 in patients with moderate-to-severe AD.

In February 2025, we announced that the last patient in Part A of the Phase 2 trial had been dosed and that we had commenced dosing of Part B.

In August 2024, we initiated a Phase 1 trial of APG990 in healthy volunteers and in March 2025, we announced positive interim safety and PK data from that trial.

In December 2024, we initiated a Phase 1 trial of APG333 in healthy volunteers.

In March 2024, we initiated a Phase 1 trial of APG808 in healthy volunteers and in December 2024, we announced positive interim safety, PK and PD data from that trial.

Our pipeline comprises four programs being developed initially for the treatment of I&I indications, as shown below.

Our programs incorporate advanced antibody engineering to optimize half-life and other properties designed to overcome limitations of existing therapies.

We believe each of our product candidates has potential for broad application across multiple I&I indications.

We have multiple clinical programs in our pipeline based on four validated targets being developed initially for the treatment of I&I indications, as shown below.

We believe each of our programs has potential for broad application across multiple I&I indications.

APG777 – anti-IL13 antibody, same mechanism of action as EBGLYSS (lebrikizumab)

APG777 is a subcutaneous (“SQ”) extended half-life monoclonal antibody (“mAb”) targeting IL-13.

In August 2023, we announced the dosing of our first participant in our first clinical trial for APG777.

In 2024, we announced positive interim safety and PK data from this trial with APG777 demonstrating a potential best-in-class PK profile, including a half-life of 77 days, supporting the potential for every three- to six- month maintenance dosing in AD.

Single doses of APG777 demonstrated a deep and sustained effect on PD markers out to approximately 12 months.

APG777 was well-tolerated across all dose groups.

In May 2024, we commenced dosing in the Phase 2 clinical trial of APG777 in patients with moderate-to-severe AD.

In February 2025, we announced that the last patient in the Part A portion of the trial had been dosed with 16-week topline data from Part A expected in mid-2025.

In February 2025, we also announced that we had commenced dosing of Part B of the Phase 2 trial.

All patients benefiting from treatment will have the opportunity to continue to APG777 maintenance treatment, which will evaluate three- to six-month dosing intervals.

We anticipate maintenance data from Part A in the first half of 2026 and 16-week topline data from Part B in the second half of 2026.

Based on our initial clinical data, we plan to advance the development of APG777 in asthma and EoE by initiating a Phase 1b trial in asthma in the first half of 2025, followed by a Phase 2b trial in asthma in the second half of 2025, and a Phase 2 trial in EoE in 2026.

Based on our clinical data, we expect to further evaluate additional opportunities to develop APG777 for other I&I indications, including alopecia areata (“AA”), chronic rhinosinusitis with nasal polyps (“CRSwNP”), chronic spontaneous urticaria (“CSU”), and prurigo nodularis (“PN”).

In addition, we plan to evaluate APG777 in combination with other investigational therapies within our pipeline to potentially enable greater efficacy for I&I conditions.

We plan to initiate our first combination study, a Phase 1b trial of APG777 and APG990, a novel, SQ, half-life extended mAb targeting OX40L, in 2025.

This combination study is designed to evaluate the coformulation of APG777 and APG990 (“APG279”) against DUPIXENT in patients with moderate-to-severe AD, with readout expected in the second half of 2026.

APG990 – anti-OX40L antibody, same mechanism of action as amlitelimab;

potential combination therapy with APG777

The agents listed above are currently under investigation.

Their safety and effectiveness have not yet been established by any regulatory authority.

APG808 (not shown) is a novel half-life extended IL-4Rα antibody.

Apogee announced positive interim results from the Phase 1b trial of APG808 in patients with mild-to-moderate asthma in May 2025.

1 APG279 is a combination of zumilokibart (APG777) and APG990.

APG279 will be co-administered in the proof-of-concept Phase 1b trial;

coformulation planned for future clinical studies and commercialization.

2 APG273 is a combination of zumilokibart and APG333.

Zumilokibart (APG777) – anti-IL13 antibody

Zumilokibart is a subcutaneous (“SQ”) extended half-life monoclonal antibody (“mAb”) targeting IL-13.

Phase 1 Trial in Healthy Volunteers

In August 2023, we initiated a Phase 1 trial of zumilokibart in healthy volunteers.

The zumilokibart Phase 1 trial was a double-blind, placebo-controlled study in healthy volunteers and consisted of a single-ascending dose (“SAD”) component and a multiple ascending dose component.

Eight healthy volunteers, six treated with zumilokibart and two treated with placebo, were enrolled in each cohort, and we enrolled a total of 40 healthy adult subjects in the trial.

In March 2024, we announced positive interim safety and PK data from this trial with zumilokibart demonstrating a potential best-in-class PK profile, including a half-life of 77 days, supporting the potential for every three- to six- month maintenance dosing in AD.

Single doses of zumilokibart demonstrated a deep and sustained effect on PD markers out to approximately 12 months.

Zumilokibart was well-tolerated across all dose groups.

APEX Phase 2 Trial for Patients with AD

In May 2024, we announced dosing of our first patient in the APEX Phase 2 clinical trial, which is a randomized, placebo-controlled study evaluating zumilokibart in patients with moderate-to-severe AD.

In July 2025, we announced positive 16-week data from the Part A portion of the APEX Phase 2 clinical trial.

Part A of the trial enrolled 123 adult patients who were randomized 2:1 to zumilokibart versus placebo and received an induction regimen dosing of 720mg at Weeks 0 and 2, followed by 360mg at Weeks 4 and 12.

The primary endpoint for the induction arm of Part A was percentage change in Eczema Area Severity Index (“EASI”) score from baseline at Week 16.

Secondary endpoints included EASI-75, EASI-90, Validated Investigator Global Assessment (“vIGA”) 0/1 and Itch Numeric Rating Scale (“NRS”) at Week 16.

In non-head-to-head trial comparisons, the initial 16-week findings from Part A included efficacy results, which compared favorably versus standard of care across endpoints, as well as rapid onset of itch relief and lesion reduction, and a favorable safety profile consistent with its class.

The Part A trial met its primary endpoint, with zumilokibart showing significantly greater least squares mean percent change from baseline at Week 16 with an EASI reduction of 71.0% compared to placebo of 33.8% (p < 0.001).

Zumilokibart showed the highest absolute and placebo-adjusted EASI-75 of any biologic in a 16-week global study with 66.9% of patients treated with zumilokibart achieving EASI-75 compared to 24.6% on placebo (p < 0.001).

Pre-specified sensitivity analysis showed consistent results in both moderate and severe patients based on baseline EASI score.

The results demonstrated a vIGA 0/1 of 34.9% compared to placebo of 17.3% (p < 0.05) and an EASI-90 of 33.9% compared to placebo of 14.7% (p < 0.05).

Treatment of patients with zumilokibart led to rapid and deep onset of itch relief and achieved a statistically significant reduction by Week 1, with a 50.7% reduction of Itch NRS from baseline compared to placebo of 23.2% (p < 0.01) at Week 16.

Zumilokibart was well tolerated, with 56.1% of zumilokibart -exposed patients experiencing treatment-emergent adverse events (“TEAEs”) (vs.

63.4% in placebo).

The most common TEAEs, occurring in more than 5% of patients, were non-infective conjunctivitis (14.6% vs.

2.4% in placebo), upper respiratory tract infection (8.5% vs 12.2% in placebo), nasopharyngitis (4.9% vs.

12.2% in placebo), and pain in extremity (0.0% vs.

7.3% in placebo) with the latter three being numerically lower in zumilokibart treated patients compared to placebo.

Serious TEAEs were rare for zumilokibart -exposed patients (1.2% vs.

2.4% in placebo).

The discontinuation rate due to adverse events was low for zumilokibart -exposed patients (2.4%).

There were no injection site reactions in the zumilokibart treated group.

In addition, improvement in asthma and sinusitis, as measured by improvements in ACQ-5 and SNOT-22 in patients with comorbid asthma or sinusitis, was observed, which reflect zumilokibart’s potential to broadly impact Type 2 inflammatory disease.

All Part A patients that benefited from treatment in the induction arm received the opportunity to continue to zumilokibart maintenance treatment, which evaluated three and six-month dosing intervals.

Patients in the placebo arm for the first 16 weeks also received the opportunity to receive an induction regimen of zumilokibart followed by three-month dosing of zumilokibart.

A schematic of the Part A trial design is shown in Figure 1 below.

We expect to report Part A maintenance data in March 2026.

Figure 1 — APEX Phase 2 Part A trial design evaluating zumilokibart in patients with AD

In February 2025, we announced that we had commenced dosing of the Part B portion of the APEX Phase 2 trial.

Part B is testing a higher and a lower dose of zumilokibart.

The APEX Part A induction regimen was designed to exceed EBGLYSS exposures by approximately 30% to 40% with potential for improved clinical outcomes and maintenance regimen is designed to equal lebrikizumab’s exposures.

The results at Week 16 of the Part A study showed that patients in the highest zumilokibart exposure quartile (n=19) achieved the highest clinical response of any quartile in a post hoc exposure-response analysis.

These patients had a mean 84.0% reduction in EASI from baseline, 89.5% of patients reaching EASI-75, 63.2% achieving IGA0/1, and 63.2% achieving EASI-90, demonstrating a robust response at the highest exposure level.

The highest zumilokibart Part B dose was designed to exceed EBGLYSS exposures by approximately 90 to 100% as show in Figure 2, which is similar to the exposure obtained in the highest quartile of the Part A results.

A schematic of the APEX Part B trial design is shown in Figure 2 below.

Figure 2 — APEX Phase 2 Part B trial design evaluating zumilokibart in patients with AD

In January 2026, we announced that we completed Part B enrollment ahead of schedule and exceeded target enrollment with a total of 347 patients.

We expect to report 16-week topline induction data from Part B in the second quarter of 2026.

Subject to positive results and regulatory alignment with the U.S.

Food and Drug Administration (the “FDA”), we plan to initiate a Phase 3 trial in AD in the second half of 2026, enabling a potential launch of zumilokibart for the treatment of AD in 2029.

Phase 1b Trial in Patients with Asthma

In April 2025, we initiated a Phase 1b trial of zumilokibart (APG777) in patients with mild-to-moderate asthma, and in January 2026, we announced positive interim data from the trial.

The trial is a double-blind, placebo-controlled trial evaluating the safety and tolerability of zumilokibart in patients with mild-to-moderate asthma.

The trial is designed to also evaluate fractional exhaled nitric oxide (“FeNO”) suppression, a biomarker of Type 2 inflammation that has shown the strongest correlation with exacerbations in asthma.

The trial enrolled 31 adult patients who were randomized 3:1 to zumilokibart versus placebo and participants received a single dose of 720 mg of zumilokibart or placebo on day 1.

Nineteen of the patients with mild-to-moderate asthma had a FeNO baseline ≥25 ppb, representative of asthma with Type 2 inflammation, and as a result met the pre-specified criteria for the analysis population.

In the trial, zumilokibart demonstrated a favorable safety profile and was well-tolerated in all patients.

In the 19 patients analysis population, the only TEAEs observed in more than one patient was gastroesophageal reflux disease (“GERD”), which was observed in 2 patients.

In the analysis population, there were no Grade 3 or higher TEAEs or serious adverse events observed and no conjunctivitis, injection site reactions, or anti-drug antibodies (“ADAs”) were observed.

In the full safety population (n=31) that were on treatment (n=23), TEAEs occurring in more than one patient on zumilokibart were upper respiratory tract infection (n=3), nasopharyngitis (n=2), GERD (n=2), and arthralgia (n=2);

there were no Grade 3 or higher TEAEs or serious adverse events.

Zumilokibart demonstrated robust and durable suppression of FeNO following a single dose in the analysis population.

A maximum absolute mean FeNO reduction of 45 ppb (60% decrease from baseline) after a single dose was observed in the analysis population.

Durable FeNO suppression through 16 weeks was observed for all patients in the analysis population.

Zumilokibart also demonstrated suppression of FeNO through 32 weeks for those patients in the analysis population with follow up available at the time of the data cut (n=3), supporting the potential for 3- or 6- month dosing.

In the trial, positive trends were observed in forced expiratory volume in one second (“FEV1”) and across Type 2 biomarkers for all available data in the analysis population.

FEV1 is a pharmacodynamic measure of

lung function.

Based on these results, we anticipate sharing our plans later in 2026 to further evaluate zumilokibart in the ASPIRE Phase 2 asthma trial.

Expansion Opportunities in Other Indications

We expect that results from the Phase 1b trial of zumilokibart for the treatment of asthma, in addition to topline induction data from the Part B portion of the APEX Phase 2 trial in AD, will allow us to determine dose selections for further expansion indications in 2027 and beyond, including but not limited to asthma and EoE.

We expect to announce plans for the Phase 2 trial in EoE in 2026.

Based on our clinical data, we expect to further evaluate additional opportunities to develop zumilokibart for other I&I indications, including alopecia areata, chronic rhinosinusitis with nasal polyps (“CRSwNP”), chronic spontaneous urticaria, and prurigo nodularis.

In addition, we plan to evaluate zumilokibart in combination with other investigational therapies within our pipeline to potentially enable greater efficacy for I&I conditions.

The first of these combinations is APG279, which combines zumilokibart with APG990, our novel, SQ, half-life extended mAb targeting OX40L.

We are also evaluating APG273, which combines zumilokibart with APG333, our novel, SQ, half-life extended mAb targeting thymic stromal lymphopoietin (“TSLP”).

APG279 – Combination of zumilokibart (APG777) and APG990 – anti-OX40L antibody

We are developing zumilokibart and APG990 together as APG279, a potential first-in-class coformulation for the treatment of AD by combining deep and sustained inhibition of Type 2 inflammation via zumilokibart’s inhibition of IL-13 with broader inhibition of Type 1-3 inflammation through APG990’s inhibition of OX40L.

APG990 is an SQ extended half-life mAb that utilizes advanced antibody engineering to target OX40L.

We plan to develop APG777 and APG990 together as a potential first-in-class coformulation for the treatment of AD by combining deep and sustained inhibition of Type 2 inflammation via APG777’s inhibition of IL-13 with broader inhibition of Type 1-3 inflammation through APG990’s inhibition of OX40L.

APG279 has been shown to retain stability, injectability, and convenience of individual components in preclinical studies.

In preclinical studies, APG279 has also demonstrated broad inhibition of Type 1, Type 2 and Type 3 inflammation, similar to what was seen with Janus kinase (“JAK”) inhibition, but with potential for better tolerability than JAK inhibitors.

We believe these combined mechanisms offer the potential for improved clinical responses over monotherapy while our planned approach of coformulating two extended half-life mAbs holds the potential for best-in-class dosing.

In August 2024, we initiated a Phase 1 clinical trial of APG990 in healthy volunteers to establish safety, tolerability and PK profile, which could enable the combination with APG777.

In March 2025, we announced positive interim safety and PK data from the APG990 Phase 1 clinical trial.

In August 2024, we initiated a Phase 1 clinical trial of APG990, which was designed as a double-blind, placebo-controlled, first-in-human, single-ascending dose trial designed to evaluate the safety and PK of APG990 in 40 healthy adult participants across five cohorts.

Doses of subcutaneous APG990 evaluated in the study included 75mg, 150mg, 300mg, 600mg and 1,200mg.

In March 2025, we announced positive interim safety and PK data from the trial.

PK data showed a half-life of approximately 60 days across doses tested.

APG990, in single doses up to 1,200mg, was well tolerated and showed a favorable safety profile, consistent with other assets targeting OX40L.

In addition, preclinical toxicology studies of the combination of APG777 and APG990 showed no findings at any dose level, including the highest dose tested of 150 mg/kg per agent.

Based on these results, we plan to submit an Investigational New Drug application or foreign equivalent for APG279.

Following clearance, we plan to initiate in 2025 a Phase 1b trial of APG279 against DUPIXENT in approximately 50 to 75 patients with moderate-to-severe AD with a data readout expected in the second half of 2026.

APG333 – anti-TSLP antibody, same mechanism of action as TEZPIRE (tezepelumab);

potential combination therapy with APG777

APG333 is a fully-human mAb against thymic stromal lymphopoietin (“TSLP”), an epithelial cell-derived cytokine that has emerged as an attractive validated target for the treatment of people living with asthma and COPD.

In preclinical studies, the combination of APG777 and APG333 has been shown to impact both central inflammation and local airway responses.

This has the potential to improve clinical outcomes compared to approved or in-development biologics which only target peripheral or central inflammation, not both, and retains the potential for a significantly less frequent dosing schedule.

In December 2024, we initiated a Phase 1 trial of APG333 in healthy volunteers and we expect interim data from the trial in the second half of 2025.

We plan to evaluate APG777 and APG333 monotherapies in respective Phase 1b trials in patients with asthma in 2025 to support advancement into future combination trials in asthma and COPD.

Subject to positive data, we plan to study APG777 in combination with APG333 to drive potential best-in-class efficacy in respiratory conditions.

APG808 – anti-IL4Rα antibody, same mechanism of action as DUPIXENT

The most common (≥10%) TEAEs were headache.

53% of participants observed at least one TEAE and there were no Grade 3 TEAEs related to study drug or severe adverse events.

No adverse events led to study discontinuation.

There were no cases of pyrexia or chills.

In July 2025, we commenced dosing in the Phase 1b trial of APG279 against DUPIXENT in patients with moderate-to-severe AD, which was upsized from approximately 50 to 80 patients due to a strong patient enrollment, with a data readout expected in the second half of 2026.

The initial clinical trial of APG279 is being conducted as a coadministration of zumilokibart and APG990.

We plan to advance the development of APG279 in future studies as a coformulation.

The PK data for APG990, when considered together with APG279 coformulation data, provides the potential for dosing the combination two to four times per year with a single 2 mL coformulated injection.

APG273 – Combination of zumilokibart (APG777) and APG333 - anti-TSLP antibody

We are developing zumilokibart and APG333 together as APG273, a potential quarterly or less frequently dosed co-formulation for the treatment of asthma and COPD.

APG333 is a fully-human mAb against TSLP, an epithelial cell-derived cytokine that has emerged as an attractive validated target for the treatment of people living with asthma and COPD, with the potential for extended half-life and to be used in combination with other mAbs for potentially greater efficacy in broader populations.

In December 2024, we initiated a Phase 1 clinical trial of APG333 in healthy volunteers, and in November 2025, we announced positive interim safety, PK and PD results from the clinical trial.

APG333 demonstrated a half-life of approximately 55 days, supporting the potential for every three- and six-month dosing.

In addition, key biomarkers of eosinophils and IL-5 showed depth of suppression in line with TSLP analogs and durability out to 6 months (limit of available follow-up).

APG333, with single doses of up to 1,000 mg, was well tolerated across the four cohorts.

The most common TEAEs occurring in ≥10% of APG333 treated participants were headache and upper respiratory tract infection.

TEAEs were generally mild and self-limited and there were no dose dependent trends in TEAEs seen.

There were no Grade 3 TEAEs or severe adverse events;

and no adverse events led to study discontinuation.

We plan to announce additional clinical plans for APG273 in 2026 to support advancement into future combination trials in asthma and COPD.

APG808 – anti-IL4Rα antibody

APG808 is an SQ extended half-life mAb targeting IL-4Rα, a target with clinical validation across eight different Type 2 allergic diseases.

4 unchanged sentences

APG808 was well-tolerated across all dose groups.

We are also now evaluating APG808 in a Phase 1b trial in patients with asthma, with data expected in the first half of 2025.

In May 2025, we announced positive interim results from the Phase 1b trial of APG808 in patients with mild-to-moderate asthma.

The trial was a double-blind, placebo-controlled, multiple-dose trial, which evaluated the safety and tolerability of APG808 in 22 adult patients with mild-to-moderate asthma.

The trial also evaluated FeNO, thymus and activation-regulated chemokine (“TARC”), and pSTAT6.

Participants were randomized 3:1, receiving 600mg of APG808 or placebo on day 1 and day 29.

The results demonstrated that APG808 was well-tolerated, with multiple doses of APG808 resulting in rapid suppression of FeNO, with a maximal robust FeNO decrease from baseline of 53% and sustained FeNO decrease from baseline of 50% at 12 weeks.

APG808 also demonstrated sustained and near-complete reduction in pSTAT6 as well as deep reduction of TARC maintained through 12 weeks.

The most common TEAEs observed were headache, injection site erythema, and upper respiratory tract infections.

There were no Grade 3 TEAEs or severe adverse events, and no adverse events led to study discontinuation.

APG808’s optimized PK profile coupled with FeNO suppression out to 12-weeks reinforces the potential for 2-months or longer maintenance dosing, offering a significant advantage compared to the current bi-weekly standard of care.

Our goal is to discover and develop new therapies for a range of I&I indications.

We aim to accomplish this goal by focusing on known biologic drivers of disease and utilizing advanced antibody engineering to develop product candidates with optimized properties that have the potential to overcome limitations of existing therapies.

For instance, each of our programs, APG777, APG990, APG333 and APG808, bind to the same epitopes, or binding sites, on IL-13, OX40L, TSLP and IL-4Rα as EBGLYSS (lebrikizumab), amlitelimab, TEZPIRE (tezepelumab), and DUPIXENT (dupilumab), respectively, based on our head-to-head preclinical studies, but are designed to include extended half-life technologies and other optimized properties.

When designing our programs, we test multiple half-life extension technologies, including YTE and LS amino acid modifications, to identify the optimal candidate to advance against each target.

For instance, each of our product candidates, zumilokibart (APG777), APG990 (as a combination partner with zumilokibart for APG279), APG333 (as a combination partner with zumilokibart for APG273) and APG808, bind to the same epitopes, or binding sites, on IL-13, OX40L, TSLP and IL-4Rα as EBGLYSS (lebrikizumab), amlitelimab, TEZPIRE (tezepelumab), and DUPIXENT (dupilumab), respectively, based on our head-to-head preclinical studies, but are designed to include extended half-life technologies and other optimized properties.

When designing our product candidates, we test multiple half-life extension technologies, including YTE and LS amino acid modifications, to identify the optimal candidate to advance against each target.

YTE amino acid modifications are a triple modification (M252Y/S254T/T256E) introduced into the antibody, while LS amino acid modifications are a double modification (M428L/N434S).

YTE and LS amino acid modifications are proven half-life extension technologies that have the potential to significantly improve the PK profile and reduce injection burden compared to existing agents.

In addition to extended half-life, our antibody engineering programs are designed to improve antibody candidate attributes, including in vitro potency, bioavailability and decreased PK variability, as well as those attributes essential for manufacturability and high concentration formulation (i.e.

In addition to extended half-life, our antibody engineering product candidates are designed to improve antibody candidate attributes, including in vitro potency, bioavailability and decreased PK variability, as well as those attributes essential for manufacturability and high concentration formulation (i.e.

viscosity, solubility and stability) to generate optimized antibodies.

We believe our approach will enable us to develop a portfolio of therapies that are differentiated compared to the currently available standards of care and address unmet medical needs for I&I indications, including the potential for improved dosing and/or efficacy.

Our goal is to become a leader in developing novel therapies for I&I indications.

We believe our approach will

enable us to develop a portfolio of therapies that are differentiated compared to the currently available standards of care and address unmet medical needs for I&I indications, including the potential for improved dosing and/or efficacy.

Our goal is to become a leader in developing and commercializing novel therapies for I&I indications.

The key elements of our strategy include:

• Advancing APG777 targeting IL-13 through clinical development and regulatory filings for AD;

• Advancing APG990 targeting OX40L and APG279 for the dual inhibition of OX40L and IL-13;

• Advancing APG333 targeting TSLP and the combination of APG777 and APG333 for the dual inhibition of TSLP and IL-13;

• Advancing zumilokibart targeting IL-13 through clinical development, regulatory filings, approval and launch for AD;

• Advancing APG279 for the dual inhibition of OX40L and IL-13;

• Advancing APG273 for the dual inhibition of TSLP and IL-13;

• Maximizing the potential of our programs through indication expansion beyond AD, including asthma, EoE and COPD;

14 unchanged sentences

It is estimated that 81.6 million people suffer from moderate to severe AD worldwide.

Approximately 40% of all patients have moderate-to-severe disease.

Approximately 40% of all AD patients have moderate-to-severe disease.

The incidence of AD has increased two- to three-fold in industrialized nations since the 1970s, with approximately 15% to 20% of children and 1% to 3% of adults affected worldwide.

8 unchanged sentences

Outcomes in AD are primarily reported using two measures:

Eczema Area and Severity Index (“EASI”) and Investigator’s Global Assessment (“IGA”).

EASI and IGA.

Other measures are used as well to gain a comprehensive understanding of a treatment’s impact on AD patients.

16 unchanged sentences

mAbs have emerged as the preferred frontline therapy in most adult and pediatric patients with moderate-to-severe AD that is not controlled by topical therapies.

There are four U.S.

Food and Drug Administration (“FDA”)-approved mAbs, DUPIXENT, ADBRY, EBGLYSS, and NEMLUVIO, labeled to treat moderate-to-severe AD that is inadequately controlled by topical corticosteroids.

DUPIXENT is indicated for the treatment of adult and pediatric patients aged six months and older with moderate-to-severe AD whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.

It can be used with or without topical corticosteroids.

DUPIXENT is a fully human mAb that inhibits the signaling of the IL‑4 and IL‑13 pathways.

For adults with AD, DUPIXENT is dosed via SQ injection with an initial loading dose requiring two injections, followed by one injection every two weeks for adults with AD.

For pediatric patients, it is dosed as one or two injections every two to four weeks depending on age and weight.

DUPIXENT was studied in over 2,800 patients across multiple pivotal trials and demonstrated clinically meaningful improvements at Week 16 in adult, adolescent and pediatric patients.

ADBRY is indicated for the treatment of moderate-to-severe AD in adult patients whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.

It can be used with or without topical corticosteroids.

ADBRY is a fully human, high-affinity mAb that targets IL13.

It selectively inhibits IL13, preventing IL13 induced immune responses in the skin.

It is dosed via SQ injection with an initial loading dose requiring either (i) in the case of prefilled syringes, four injections, followed by two injections every two weeks for 16 weeks then, for select patients, maintenance injections every month may be considered;

or (ii) in the case of

autoinjectors, two injections, followed by one injection every two weeks for 16 weeks then, for select patients, maintenance injections every month may be considered.

ADBRY was evaluated in nearly 2,000 patients with AD in three pivotal trials.

Across the three trials, ADBRY demonstrated improvements in both skin clearance and lesion extent and severity at Week 16.

EBGLYSS is indicated for the treatment of moderate-to-severe AD in adult patients whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.

It can also be used with or without topical corticosteroids.

EBGLYSS is designed to inhibit the IL-13 pathway.

In three Phase 3 clinical trials, SQ administration of EBGLYSS was dosed every two weeks in the induction phase (first 16 weeks of treatment) and every two or four weeks in the maintenance phase (from 16 weeks to 52 weeks).

EBGLYSS met all primary and key secondary endpoints at Week 16 in Phase 3 trials.

The most commonly reported adverse events (“AEs”) were conjunctivitis, common cold and headache.

In Phase 3 studies, ~30% higher exposure was seen in the low body weight group (less than 60kg), which also had numerically higher efficacy than the overall study population across all key endpoints, including EASI-75 and more stringent endpoints such as EASI-90 and IGA 0/1.

NEMLUVIO is indicated for the treatment of moderate-to-severe AD patients aged 12 and over in combination with topical corticosteroids and/or calcineurin inhibitors when the disease is not adequately controlled with topical prescription therapies.

NEMLUVIO is a humanized IgG2 mAb that inhibits IL-31 signaling by binding selectively to IL-31Rα.

It is dosed via SQ injection with an initial loading dose requiring two injections, followed by one injection every four or eight weeks in maintenance.

NEMLUVIO was evaluated in combination with topical corticosteroids and/or calcineurin inhibitors in over 1,700 patients with AD in two pivotal trials.

Across the two trials, NEMLUVIO in combination with topical corticosteroids and/or calcineurin inhibitors demonstrated improvements in both skin clearance and lesion extent and severity at Week 16.

There are four FDA approved mAbs, DUPIXENT, ADBRY, EBGLYSS, and NEMLUVIO, labeled to treat moderate-to-severe AD that is inadequately controlled by topical corticosteroids.

For patients for which biologics such as DUPIXENT, ADBRY, EBGLYSS, or NEMLUVIO do not provide adequate control of moderate-to-severe AD, systemic JAK inhibitors may be recommended.

4 unchanged sentences

These toxicity challenges have limited clinical use of systemic JAK inhibitors for AD where patients are generally healthy and young.

Systemic JAK inhibitors represented just 7% of the AD market in 2022.

In 2025, systemic JAK inhibitors represented approximately 10% of the AD market based on revenue.

An emerging mechanism in treatments for AD is targeting OX40L, which occurs higher up in the inflammatory pathway than IL‑13 or IL‑4Rα and potentially broadens the impact on the inflammatory cascade.

OX40L is the ligand for OX40.

Amlitelimab, which targets OX40L, has demonstrated activity in Phase 2 trials in AD.

For additional information on AD treatments currently available or in development, see the section titled “—Competition” below.

Addressing the Limitations of Current Biologics

5 unchanged sentences

Pediatric patients in particular often suffer from fear of needles, which limits the use of current biologics in a large and growing patient population.

In 2023, we conducted a single-blinded market research survey of 25 practicing dermatologists in 14 states in the United States, with the assistance of an expert search network.

Dermatologists were selected based on years of experience in the field (four or more years of practice post residency or fellowship training), number of AD patients treated (30 or more AD patients seen per month), experience prescribing biologic therapies in AD (10% or more of AD patients on biologics) and no previous contact with us.

We conducted approximately 30‑minute interviews using standardized questions to solicit sentiments towards a potential new product offering with every three-month dosing in maintenance and the same efficacy and safety as DUPIXENT, which was presented as a blinded Target Product Profile (“TPP”).

The dermatologists selected for the survey have an average of 20 years in practice, treat an average of 88 AD patients per month and see a mix of both adult and pediatric patients.

In the interviews, dermatologists described how they would incorporate the TPP in treatment algorithms for biologic naïve patients (i.e., patients who have never taken a biologic treatment, but qualify based on failure to topical therapies) and biologic-experienced patients (i.e., patients who are either currently or have previously used a biologic therapy for AD).

On average, dermatologists indicated they expect that approximately 92% of their biologic patients would start a product with the TPP as frontline treatment.

For patients currently or previously on biologic therapy, dermatologists estimated approximately 57% would switch to a product with the TPP.

Likewise, patients were given APG777 TPP and two other available treatments.

When asked their preference, 94% of patients preferred a Q3M dosing regimen.

Finally, payers were asked how they might cover a product with the TPP, at a similar net price, and most see this product as a first line biologic product.

Dermatologists were then asked how their intent to use a product with the TPP would change if (i) it was dosed every two months in the maintenance setting, or (ii) it was dosed every six months in the maintenance setting.

As shown in Figure 3 below, results for the every two-month dosing were consistent with the every three month dosing.

With every two-month dosing, dermatologists on average indicated they would prescribe a product with the TPP to 91% of their biologic naïve patients and they estimated 56% of their patients currently or previously on biologic therapy would switch to a product with the TPP.

As shown in Figure 3 below, results for the every six-month dosing showed a greater proportion of patients would switch from a current biologic than for the every three-month dosing.

With every six-month dosing, dermatologists on average indicated they would prescribe a product with the TPP to 91% of their biologic naïve patients and they estimated 68% of patients currently or previously on biologic therapy would switch to a product with the TPP.

Figure 3 — Intent to use a product with the APG777 Target Product Profile with every three- or six-month maintenance dosing and equivalent efficacy and safety to DUPIXENT

We are not aware of any programs in development in AD that have the potential to reduce dosing frequency past four weeks and the related burden of administration on patients.

A more convenient dosing schedule is especially important for pediatric patients, which has the potential to expand the market significantly.

In 2025, we conducted, through an independent third-party, a blinded market research survey of 75 practicing healthcare professionals (“HCPs”) comprised of dermatologists, allergists, and immunologists in the United States.

HCPs surveyed were screened for years of experience in the field, number of AD patients treated, and experience prescribing biologic therapies in AD.

The HCPs that responded to the survey had an average of 16 years in practice, treated an average of 100 AD patients per month and treated a mix of both adult and adolescent patients.

The research included a survey aimed at understanding HCP perceptions and preferences on the current AD biologic market as well as a potential new treatment option with every three-month dosing in maintenance.

We created a blinded Target Product Profile (“TPP”) comprised of a potential indication statement and, dosing regimen, as well as efficacy and safety outcomes based the on zumilokibart (APG777) APEX Part A 16-week induction data.

Respondents were presented with TPPs for each of the currently marketed AD biologic treatments as well as a blinded TPP for zumilokibart.

The blinded zumilokibart TPP was ranked as the most preferred biologic treatment by 60% of the respondents, and 79% of respondents indicated they would consider the blinded zumilokibart TPP their biologic of choice for the treatment of their moderate to severe AD patients.

For those patients treated with the leading currently approved biologic for the treatment of moderate to severe AD and not well-controlled, 79% of HCPs expressed they were likely to prescribe the blinded zumilokibart TPP.

In 2025, we also conducted an independent blinded market research survey of 90 moderate to severe AD patients in the United States.

The respondent pool consisted of 30 patients who had never been treated with a biologic, 30 biologic-treated AD patients that were well controlled, and 30 biologic-treated patients that were not well controlled on their current treatment.

All patients had to be pharmacologically treated for at least four months by a dermatologist, allergist or immunologist for their AD.

The research included a survey aimed at understanding patient perceptions of the current AD treatment options and what dosing, clinical, and safety attributes are most important in a treatment.

Similar to the HCP research, we created and presented a blinded TPP comprised of a potential indication statement and dosing regimen, as well as efficacy and safety outcomes based on the zumilokibart APEX Part A 16-week induction data.

The biologic naïve patient subgroup was asked about their likelihood of starting a biologic treatment if the blinded zumilokibart TPP was available on the market.

67% of the biologic naïve patients expressed a likelihood of starting biologic treatment.

The biologic treated subgroups (well controlled and not well controlled), were asked about their likelihood of switching to the blinded zumilokibart TPP from their current medication if it were available on the market.

97% of the not well controlled patient respondents expressed they were likely to switch, and 90% of the well-controlled patient respondents expressed they were likely to switch.

Patient respondents highlighted perceived efficacy data on skin clearance and itch, side effect profile, and once every three months maintenance dosing as reasons to consider starting or switching to the blinded zumilokibart TPP.

Overview of Asthma

2 unchanged sentences

Asthma is estimated to affect 40 million adults and 12 million children in the United States, France, Germany, Italy, Japan, Spain and the United Kingdom, with prevalence rates of 5% to 8% in many countries.

Currently, the asthma market is greater than $10 billion in these seven major markets.

The global asthma biologics market is forecasted to grow to approximately $16B by 2028.

Asthma is a complex multifactorial disease, attributed to interactions between genetic susceptibility, host factors and environmental exposures, which result in airway inflammation, control of airway tone and reactivity.

1 unchanged sentence

In the United States, asthma accounts for approximately five million physician visits, one million emergency room visits and thousands of deaths annually.

We believe asthma to be an important expansion opportunity for zumilokibart given the significant overlap with AD (31% according to third-party market research studies) and unmet need for extended dosing biologics that do not sacrifice clinical benefit.

Patients with moderate-to-severe asthma who qualify and require biologic treatment have a serious condition that, when not treated appropriately, can lead to additional exacerbations and unnecessary emergency room and hospital visits.

Extended duration therapies may lead to increased adherence rates with better control and outcomes for these patients.

Eosinophilic asthma is a recognized subtype associated with increased severity and late-onset asthma.

IL-13 can induce immune activation and eosinophilic response broadly, and in the case of asthma, contribute to inflammation, airway hyperreactivity and recruitment of eosinophils to lung tissues.

Further, in third-party clinical studies, IL-13 and eosinophils have been shown to be positively correlated in airway lumen.

Thus, we believe targeting IL-13 in eosinophilic asthma is a compelling approach.

Overview of Current Treatment Options

2 unchanged sentences

Biologics, specifically, have begun to play an important role in the treatment of moderate-to-severe asthma, largely as an add-on to inhaled medication.

XOLAIR was the first biologic approved for asthma in 2003 and subsequently, an additional five biologics have been approved since 2015 (NUCALA, CINQAIR, FASENRA, DUPIXENT and TEZSPIRE).

All have shown reductions in annualized exacerbation rates of approximately 50% to 60% and are dosed every two to eight weeks.

XOLAIR was the first biologic approved for asthma in 2003 and subsequently, an additional five biologics have been approved since 2015 (NUCALA, CINQAIR, FASENRA, DUPIXENT, TEZSPIRE and EXDENSUR).

For additional information on asthma treatments that are currently available or in development, see the section titled “—Competition” below.

Overview of Eosinophilic Esophagitis

6 unchanged sentences

The only available biologic for the treatment of EoE is DUPIXENT, which was first approved for this indication in 2022 and later approved for patients aged 1 and older in 2024, and requires weekly dosing.

DUPIXENT’s approval in EoE further supports the scientific rationale for IL-13/IL-4Rα targeting agents in treating EoE.

DUPIXENT was studied in approximately 300 EoE patients across two pivotal trials and demonstrated clinically meaningful improvements in histological remission defined as peak esophageal intraepithelial eosinophil count in adult, adolescent, and pediatric patients.

In adults and adolescents, DUPIXENT demonstrated clinically meaningful reduction in dysphagia symptoms as measured by reduction in Dysphagia Symptom Questionnaire score.

In pediatric patients (1-11 years of age), DUPIXENT demonstrated clinically meaningful reduction in symptoms as measured by reduction in Pediatric EoE Sign/Symptom Questionnaire-Caregiver score.

Overview of COPD

1 unchanged sentence

COPD is a heterogenous, progressive respiratory condition characterized by cough, dyspnea and airflow obstruction.

It is estimated that approximately 10% of the global population 40 years of age and older have COPD, and in 2019 (prior to the COVID–19 pandemic), COPD was the third leading cause of death globally.

It is estimated that approximately 10% of the global population 40 years of age and older have COPD, and as of 2024, COPD was the fourth leading cause of death worldwide according to the World Health Organization.

In the United States, over 150,000 people die of COPD each year.

3 unchanged sentences

For patients with refractory COPD, treatment options include chronic antibiotic use and DALIRESP (roflumilast).

A pooled analysis from two Phase 3 trials of DALIRESP in COPD patients 40 years of age and older with severe airflow limitation, bronchitis symptoms and a history of exacerbations showed a 17% reduction in moderate or severe exacerbations.

In 2024, the FDA approved DUPIXENT as the first biologic treatment for add-on maintenance for inadequately controlled COPD and an eosinophilic phenotype.

Two Phase 3 studies demonstrated that DUPIXENT dosed every 2 weeks reduced exacerbations by an average of 31% compared to placebo in patients with elevated peripheral eosinophils (≥300 cell/μL).

TEZSPIRE (tezepelumab) is a biologic being developed in COPD.

Tezspire dosed as 420 mg monthly, showed a 37% reduction in annualized exacerbations in a subset (n=92) of moderate to very severe COPD patients with eosinophils ≥150 cell/μL in an initial Phase 2 trial.

OHTUVAYRE (ensifentrine), a twice daily nebulized treatment for moderate to severe COPD, was approved in 2024.

However, the trials did not require a recent history of exacerbations.

Despite these recent advancements in COPD treatment, a significant number of patients continue to suffer and die from the disease.

Given the complexity of COPD, we believe biologics targeting Th2 immune response in patients with high peripheral eosinophils show the greatest promise, as supported by DUPIXENT’s approval in COPD and TEZSPIRE’s encouraging Phase 2 data in COPD.

Our Solution:

Building Differentiated Biologics

We are engineering therapies for AD, asthma, EoE, COPD, and other related I&I indications.

Our programs, APG777, APG990, APG333 and APG808, target IL-13, OX40L, TSLP, and IL4Rα, respectively, and are designed to overcome limitations of frequent dosing associated with currently available treatments.

We believe that each of our programs has potential for broad application across multiple I&I indications, including the potential for higher efficacy either through an improved monotherapy or via rationale combinations.

Despite advances in care, there is still high unmet medical need for patients suffering from the I&I indications that we are targeting, both in terms of reduced injection burden as well as improved efficacy.

Our programs incorporate advanced antibody engineering approaches, and are designed to optimize for half-life extension, in vitro potency, bioavailability and decreased PK variability, as well as those attributes essential for manufacturability and high concentration formulation (i.e.

viscosity, solubility and stability), potentially improving on each of those qualities over existing, non-optimized antibodies.

We utilize and test a number of half-life extension technologies, including YTE and LS, to identify the optimal candidate to advance against each target.

YTE amino acid modifications are a triple modification (M252 Y /S254 T /T256 E ) introduced into the antibody, while LS amino acid modifications are a double modification (M428 L /N434 S ).

APG777, leverages YTE amino acid modification half-life extension technology and is an SQ mAb targeting IL-13.

APG777 demonstrated a 77-day half-life in a Phase 1 clinical trial in healthy volunteers.

We initiated a Phase 2 clinical trial in patients with moderate-to-severe AD in May 2024.

The Phase 2 trial is designed to combine the

typical Phase 2a and 2b portions of a clinical trial into a single protocol.

In February 2025, we announced that the last patient in the Part A portion had been dosed and that we had commenced dosing of the Part B portion.

We anticipate maintenance data from Part A in the first half of 2026 and 16-week topline data from Part B in the second half of 2026.

APG990, leverages half-life extension technology and is an SQ mAb targeting OX40L.

We initiated a Phase 1 clinical trial of APG990 in healthy volunteers in August 2024 and announced positive interim safety and PK data in March 2025.

In 2025, we plan to initiate a Phase 1b trial designed to evaluate APG279 against DUPIXENT in approximately 50 to 75 patients with moderate-to-severe AD with a data readout expected in the second half of 2026.

APG333, leverages half-life extension technology and is an SQ mAb targeting TSLP.

We initiated a Phase 1 clinical trial of APG333 in healthy volunteers in December 2024 and expect a data readout in the second half of 2025.

Subject to positive data and required regulatory approvals, we plan to evaluate the combination of APG777 and APG333.

APG808, leverages half-life extension technology and is an SQ mAb targeting IL-4Rα.

We initiated a Phase 1 clinical trial of APG808 in March 2024 and announced positive interim safety, PK and PD data in December 2024.

We are also now evaluating APG808 in a Phase 1b trial in patients with asthma, with data expected in the first half of 2025.

The only available biologics for the treatment of COPD are DUPIXENT and NUCALA, which was approved in 2024.

For additional information on COPD treatments that are currently available or in development, see the section titled “—Competition” below.

Additional Expansion Opportunities

We believe that each of our product candidates has the potential to treat multiple additional I&I indications beyond AD, asthma, EoE and COPD, including Alopecia Areata, CRSwNP, Chronic Spontaneous Urticaria, and Prurigo Nodularis.

Initial structured indication prioritization has identified asthma as a leading expansion opportunity given the significant overlap with AD and the clinical unmet need for extended dosing biologics that do not sacrifice clinical benefit.

We may expand into additional I&I indications that are implicated in the disease pathways targeted by our current or future product candidates.

We do not yet have clinical data showing the ability of our product candidates to treat indications beyond AD and asthma and there can be no assurance that our product candidates will have similar or comparable results to any products or later-stage product candidates for these indications.

Half-Life Extension and Antibody Engineering Technologies

Our antibody engineering programs are designed to improve antibody candidate attributes, including half-life extension, in vitro potency, bioavailability and decreased PK variability, as well as those attributes essential for manufacturability and high concentration formulation (i.e.

Our antibody engineering product candidates are designed to improve antibody candidate attributes, including half-life extension, in vitro potency, bioavailability and decreased PK variability, as well as those attributes essential for manufacturability and high concentration formulation (i.e.

viscosity, solubility and stability) to generate optimized antibodies.

Each of our programs utilize YTE or LS amino acid modifications and are designed to significantly extend the half-life of antibodies by supercharging the body’s innate recycling mechanism for antibodies.

Each of our product candidates utilize YTE or LS amino acid modifications and are designed to significantly extend the half-life of antibodies by supercharging the body’s innate recycling mechanism for antibodies.

Antibodies in circulation are naturally taken up by cells and degraded, which limits the half-life in circulation.

18 unchanged sentences

The typical half-life for an IgG antibody is typically 11 to 30 days.

By contrast, IgG antibodies with half-life extension amino acid modifications, such as YTE, have the potential to increase human half-life three-to four-fold compared to non-YTE mAbs, with half-lives observed to often exceed 100 days in third-party trials.

By contrast, IgG antibodies with half-life extension amino acid modifications, such as YTE, have the potential to increase human half-life several fold compared to non-YTE mAbs, with half-lives for our first four YTE mAb product candidates having demonstrated to range from 55 days to 77 days.

The half-life extension allows the drug to remain in the body for a longer period of time and therefore have additional action.

1 unchanged sentence

• Decreased variability in drug exposure from person to person, leading to the potential for more consistent clinical outcomes.

For example, the magnitude of half-life extension that YTE amino acid modification confers has been observed to be relatively consistent from person to person in third-party trials.

The magnitude of half-life extension that YTE amino acid modification confers has been observed to be relatively consistent from person to person in third-party trials.

For this reason, the typical factors that can vary amongst different people and give rise to variability in drug exposure from person to person have less of an impact for YTE antibodies.

1 unchanged sentence

Half-life extension amino acid modifications, such as YTE and LS amino acid modifications, have been introduced to monoclonal IgG1 in a wide variety of human therapeutics.

YTE amino acid modifications have been introduced in numerous mAbs in late-stage ongoing clinical trials (e.g., depemokimab) and completed trials (e.g., motavizumab-YTE and ziltivekimab), as well as one approved product, BEYFORTUS.

The targets of these antibodies include cytokines (IL‑5 for depemokimab and IL‑6 for ziltvekimab) and viruses (RSV for motavizumab-YTE and BEYFORTUS).

Similarly, LS amino acid modifications have been introduced into numerous mAbs in early-and late-stage clinical trials (e.g., VIR‑7831, VIR‑2482 and VRC01LS) as well as approved products (e.g., ULTOMIRIS and XEVUDY).

The targets of these antibodies include complement (C5 for ULTOMIRIS) and viruses (SARS-CoV‑2 for XEVUDY, HbsAg for VIR‑2482 and HIV for VRC01LS).

The safety and immunogenicity profile of YTE-or LS-modified mAbs compares favorably to non-YTE or non-LS modified mAbs with identical targets

For example, in third-party clinical trials, the safety profile of motavizumab-YTE was comparable to that of the parent antibody, motavizumab, with no significant difference in the occurrence of self-limited AEs.

Similarly, a Phase 1 trial of depemokimab, an anti-IL‑5 with a YTE amino acid modifications for half-life extension, was notable for its overall benign safety profile and similar AE rate compared to mepolizumab (NUCALA), an anti-IL‑5 without half-life extension.

Finally, among infants with prematurity or other RSV risk factors, serious adverse event (SAE) frequency and type were comparable between nirsevimab (YTE) and palivizumab (non-YTE)-dosed infants.

In human subjects, we are not aware of administration of mAbs bearing YTE amino acid modifications being associated with greater immunogenicity than unmodified mAbs.

For example, similar levels of anti-drug antibodies (ADAs) have been measured in motavizumab as compared to motavizumab-YTE.

As another example, nirsevimab, a mAb with YTE amino acid modifications targeting RSV, exhibited lower levels of ADAs than an antibody for the same target without YTE amino acid modifications (palivizumab).

Similarly, administration of mAbs bearing LS amino acid modifications does not appear to confer any additional safety risk or immunogenicity risk.

For example, ULTOMIRIS (ravulizumab) is an LS modified version of SOLIRIS (eculizumab).

In third-party clinical trials, the AE profile of ULTOMIRIS and SOLIRIS were shown to be a similar in a head-to-head study and one ADA-positive sample was found in each treatment arm.

APG777 leverages YTE amino acid modifications half-life extension technology and is an SQ mAb targeting IL-13.

We are evaluating APG777 in AD, and plan to evaluate APG777 in a number of expansion indications, including asthma and EoE and in combination with certain of our other programs.

In our head-to-head preclinical studies of APG777 and lebrikizumab in non-human primates (“NHPs”).

APG777 showed a significantly longer half-life than lebrikizumab.

In these studies, APG777’s half-life was 27.6 days, as compared to 18.0 days for lebrikizumab based on cumulative fit models across SQ and IV groups for each compound.

In 2024, we announced interim safety, PK and PD data from our Phase 1 trial of APG777 in healthy volunteers.

PK data showed a half-life of 77 days across doses tested.

Generally, the half-life of mAbs is consistent between healthy volunteers and patients since mAbs are degraded by endogenous catabolic processes and are not subject to the same drug-drug interaction potential of many traditional small molecules.

Consequently, this gives us confidence that the PK parameters derived from the Phase 1 trial in healthy volunteers can be used to effectively model dosing regimens in the subsequent Phase 2 and Phase 3 safety and efficacy trials in patients with AD and other I&I indications.

We are testing three- and six-month dosing in our Phase 2 clinical trial of APG777.

Compared to more frequent dosing schedules associated with existing AD therapies, every three- or six-month dosing, should our clinical trials be successful in demonstrating the requisite efficacy and safety profile, has the potential to be significantly more convenient for patients, enabling them to better adhere to their dosing schedule.

Additionally, every three- or six-month dosing improves quality of life given that many patients experience “needle fatigue” and pediatric patients in particular often suffer from fear of needles.

APG777’s target, IL‑13, has no known non-disease function

APG777’s target, IL‑13, is a cytokine with no known non-disease function such as growth or metabolism.

Zumilokibart (APG777)

Zumilokibart leverages YTE amino acid modifications half-life extension technology and is an SQ mAb targeting IL-13.

Zumilokibart ’s target, IL13, has no known non-disease function

Zumilokibart’s target, IL‑13, is a cytokine with no known non-disease function such as growth or metabolism.

IL-13 is a cytokine primarily produced by activated Th2 cells.

7 unchanged sentences

Genetic factors associated with AD include variations in genes that regulate the immune response, such as those encoding for IL‑4, IL‑13 and IL‑31.

AD is characterized by a Th2 response, which describes Th2 cells, a subset of white blood cells, that produce small proteins called cytokines, like IL‑13, which regulate inflammation, immune response and tissue repair.

AD is characterized by a Th2 response, which describes Th2 cells, a subset of white blood cells, that produce small proteins called cytosine, like IL‑13, which regulate inflammation, immune response and tissue repair.

Overactivation of Th2 cells contributes to several allergic diseases, including AD, and chronic dysregulation of cytokine production and signaling leads to chronic inflammation and skin barrier dysfunction in AD.

9 unchanged sentences

In turn, the active IL-13Rα1-IL4Rα heterodimer, through a signaling cascade, leads to skin barrier defects, immune cell recruitment, tissue inflammation, lichenification (skin thickening) and pruritis (skin itching).

APG777 is designed to interrupt the heterodimer formation and thus disrupt IL-13 signaling as shown in Figure 6 below.

Figure 6 — APG777 is designed to disrupt IL-13 signaling by preventing the formation of the IL-13Rα1-IL4Rα heterodimer

In addition to AD, elevated IL‑13 has been observed in other inflammatory conditions such as asthma, CRSwNP and EoE.

Epitope, or binding site, is key in preventing the IL‑13R α 1‑IL‑4R α active heterodimer formation

As previously described, IL‑13 signaling begins with the binding of IL‑13 to IL‑13Rα1, forming an inactive complex that then binds to IL‑4Rα to form the complete, active receptor heterodimer.

This active receptor heterodimer is key to the pathogenesis of AD.

Therefore, we believe a therapeutic approach for AD needs to prevent the formation of this heterodimer.

As shown in Figure 7 below, a 3D rendering of human IL‑13 generated from our head-to-head preclinical studies described below, the dark blue highlights the epitope, or binding site, of lebrikizumab, which overlaps with APG777’s epitope, also highlighted in blue.

Importantly, these epitopes also overlap with the IL‑4Rα epitope on IL‑13.

Thus, we believe mAb binding to this location is likely to prevent the formation of the IL-13Rα1‑IL‑4Rα active heterodimer, limiting the inflammatory signaling that is key to AD pathogenesis as well as the pathogenesis of other I&I conditions.

This contrasts with the epitope of ADBRY, highlighted in gray, which does not overlap with the IL‑4Rα epitope on IL‑13 and therefore we believe may have a more limited ability to prevent heterodimerization.

Figure 7 — 3D rendering of human IL‑13 and epitopes for antibodies and receptors that bind to IL‑13

Furthermore, IL‑13 also binds a second receptor, IL‑13Rα2.

Often described as a “decoy” receptor, IL‑13Rα2 has a limited cytoplasmic domain and does not appear to mediate signal.

IL‑13Rα2 does, however, bind to IL‑13 with very high affinity, effectively removing IL‑13 from circulation.

Third-party studies involving IL-13Rα2 knockout mice demonstrated worsened atopic features, including fibrosis and itch.

ADBRY, but not lebrikizumab or APG777, has an epitope that inhibits the binding of IL‑13 to IL‑13Rα2, which could lead to increased circulating IL‑13 levels and, in a counterproductive fashion, worsen AD.

However, there can be no assurance that our programs targeting IL‑13 will not have similar or comparable results to other third-party agents based on epitope.

IL‑13 is a soluble cytokine which exists at low concentrations in circulation, making it highly amenable to half-life extension

Half-life for antibodies is a product of degradation or elimination through three pathways:

pinocytosis, target-mediated drug disposition (TMDD) and receptor-mediated endocytosis.

• Pinocytosis is a non-specific process in which extracellular fluid and substances are brought into the cell, resulting in an internalized vesicle.

This internal vesical then fuses with lysosomes.

All antibodies are subject to this elimination pathway.

• TMDD is a receptor-mediated endocytosis process, meaning that the interactions of the antibody with the receptor on the cell surface results in the internalization of the antibody and subsequent degradation via lysosomes, specialized organelles, or areas within the cell that degrade molecules and other biomaterial.

Only mAbs with receptor targets, such as APG808, which targets IL‑4Rα, are subject to this elimination pathway.

mAbs with soluble targets, such as APG777, which target the soluble cytokine IL‑13, are not eliminated via TMDD.

• Receptor-mediated endocytosis is the binding of antibodies to Fc-gamma-receptors, which are present on many immune cells, can also trigger an elimination process similar to TMDD.

However, third-party preclinical studies have demonstrated that this degradation pathway plays only a minor role in the elimination of antibodies, if at all.

Importantly, antibody recycling through FcRn only impacts degradation via pinocytosis and has no impact on elimination via TMDD.

Half-life extension through YTE amino acid modifications, which increases affinity for FcRn, therefore increasing recycling and antibody half-life, is more limited for receptor targets than soluble targets.

This is because mAbs with receptor targets are subject to TMDD in addition to pinocytosis.

Therefore, we believe soluble targets, like IL‑13, which APG777 has been engineered to target, have potential for the longest half-life extension with YTE amino acid modifications.

However, there can be no assurance that soluble targets will have such results.

APG777 and lebrikizumab have the same epitope on IL‑13 in our head-to-head preclinical studies

Epitope binning describes a technique that characterizes whether two antibodies specific to the same target (in this case, IL‑13) can each bind the target at the same time.

mAb pairs are binned together if they block each other’s ability to bind to the target antigen.

mAb pairs that are found to bin together typically bind to the same or similar epitopes on the antigen.

To characterize the binning of APG777 and lebrikizumab, we studied APG777 and lebrikizumab in head-to-head preclinical studies.

Lebrikizumab was immobilized to a sensor chip surface capable of measuring mAb-antigen interactions.

IL‑13 was first injected into the flow channel, where binding of IL‑13 to lebrikizumab generated a response.

APG777 was then subsequently injected into the flow channel and the interaction response was recorded.

In these studies, no response was observed after APG777 injection.

This indicated that APG777 and lebrikizumab binned together and provided evidence to support that the two mAbs likely bind to a similar or the same epitope, or binding site, on IL‑13.

In our similar head-to-head preclinical study, ADBRY was found to have a binding response, suggesting that it has a different epitope on IL‑13 than lebrikizumab.

APG777 matched the in vitro potency of lebrikizumab and dupilumab across all relevant assays in our head-to-head preclinical studies

APG777 was engineered to demonstrate similar preclinical activity to available therapies in our head-to-head studies.

Specifically, several assays were used to assess not only affinity for binding to IL‑13, but downstream functional inhibition of the IL‑13/IL‑4 pathway, meaning after IL‑13Rα1‑IL‑4Rα heterodimerization.

Measuring downstream functional inhibition of the pathway is critical as this measures the mAb’s impact not only on IL‑13, but also the impacts of the resulting inflammatory cascade that causes the features, signs and symptoms associated with AD.

To measure these parameters, APG777 was tested in vitro across four assays:

Human Affinity by SPR, Inhibition of pSTAT6 Induction, Inhibition of TF‑1 Proliferation and Inhibition of TARC Secretion.

These assays are described in detail below and outputs are measured in IC90, the concentration or amount of drug it takes to cause a 90% inhibition in the assay.

Results from our head-to-head preclinical studies demonstrated that each of ADBRY, lebrikizumab and APG777 had similar affinity for IL‑13.

Notably, since DUPIXENT does not target IL‑13, it cannot be compared in this assay, but can be tested in assays on pSTAT6, TF‑1 proliferations and TARC release as these assays measure inhibition in the IL‑13/IL‑4 pathway downstream.

On these assays, DUPIXENT, lebrikizumab and APG777 all showed similar inhibition, whereas ADBRY showed inferior downstream inhibition, as demonstrated by the higher IC90, which suggests greater drug concentrations are needed to obtain the same in vitro potency.

This provides preclinical evidence of similar in vitro potency among DUPIXENT, lebrikizumab and APG777 across a variety of in vitro assays.

APG777 Preclinical Dosing

APG777 has demonstrated significantly extended half-life in NHPs

In our head-to-head studies of APG777 and lebrikizumab in NHPs, APG777 showed a significantly longer half-life than lebrikizumab.

In these studies, APG777’s half-life was 27.6 days, as compared to 18.0 days for lebrikizumab, based on cumulative fit models across SQ and IV groups for each compound.

An Extensive Nonclinical Program Has Been Completed to Characterize the Toxicology, Toxicokinetics and ADA Profile of APG777 in NHPs

After evaluating APG777 across a broad range of species, NHPs represented the only pharmacologically relevant species for evaluation.

Studies were conducted using an SQ route of administration, as this is the intended route of human administration.

Three general toxicology studies with APG777 were designed to assess the toxicology, toxicokinetics and presence of ADAs in NHPs.

These included a single-dose non-GLP dose-range finding study, as well as 29-day and six-month GLP toxicology studies.

Our single-dose non-GLP study in NHPs was conducted to select doses for the subsequent one-month and six-month studies in NHPs.

No adverse findings were observed at doses up to the maximum feasible dose and the highest dose tested.

We have conducted a 29‑day repeat-dose, GLP-compliant toxicology study in NHPs, in support of our Phase 1 clinical trial in healthy volunteers.

NHPs (three to five animals per sex per group) were administered APG777 weekly (five doses in total) at 0, 30, 75 or 150mg/kg/dose via SC administration.

No adverse findings were observed up to the highest dose tested (150mg/kg), which was the maximum feasible dose and was considered the no observed adverse effect level (NOAEL) in this study.

In support of dosing in clinical trials longer than one month in duration, we completed a six-month GLP-compliant toxicology study in NHPs.

NHPs (three to five animals per sex per group) were administered APG777 weekly (27 doses in total) at 0, 30, 75 or 150mg/kg/dose via SC administration.

No adverse findings were observed up to the highest dose tested (150mg/kg), which was the maximum feasible dose and was considered the NOAEL in this study.

We believe the results of this study will support progression from Phase 1 to Phase 2 trials of extended duration.

APG777 Development

Phase 1 Trial in Healthy Volunteers

In August 2023, we initiated a Phase 1 trial of APG777 in healthy volunteers.

The APG777 Phase 1 trial was a double-blind, placebo-controlled study in healthy volunteers and consisted of a single-ascending dose (“SAD”) component and a MAD component.

Eight healthy volunteers, six treated with APG777 and two treated with placebo, were enrolled in each cohort, and we enrolled a total of 40 healthy adult subjects in the trial.

In March 2024, we announced positive interim safety and PK data and, in October and December 2024, we announced positive updated data from this trial.

Interim PK data for APG777 showed a half-life of 77 days across doses tested and PD data showed near complete inhibition of key AD biomarker pSTAT6 for approximately twelve months after a single administration and sustained TARC inhibition.

Results from the trial exceeded our trial objectives and support the potential for APG777, a novel anti-IL-13 antibody, to optimize exposure levels in 16-week induction and be dosed once every three or six months in maintenance.

These findings represent the potential for improved clinical responses from greater exposures in induction and significantly less frequent dosing in maintenance compared to currently approved monotherapy biologic therapies, which are dosed at every two to four weeks, a potential major advancement for patients with AD and other inflammatory diseases.

APG777’s PK differentiation supports further development of APG777 as a treatment for moderate-to-severe AD and other inflammatory diseases.

APG777’s PK profile supports testing higher exposures of drug in induction to potentially achieve improved clinical responses;

and testing of maintenance dosing of every three or six months,

representing two to four injections per year compared to the current treatment paradigm of 13 to 26 injections per year.

Dose-proportional increases in serum concentrations and key parameters (e.g., C max , AUC) were observed in the Phase 1 trial.

PK was generally consistent across subjects with low variability.

Single doses of APG777 demonstrated a deep and sustained effect on PD markers for approximately twelve months.

As shown in Figure 8 below, single doses of APG777 suppressed pSTAT6, one of the first downstream markers of IL-13 pathway inhibition, with near-complete inhibition (both in terms of median and mean percent change from baseline) for approximately twelve months.

Figure 8 — Mean percent pSTAT6 inhibition data for APG777 from our Phase 1 trial

As shown in Figure 9 below, single doses of APG777 suppressed TARC, an inflammatory mediator and the most strongly correlated biomarker to AD severity, with deep and sustained inhibition for approximately three months.

Figure 9 —TARC inhibition data for APG777 from our Phase 1 trial in 6 healthy volunteers receiving a single SC injection of 300mg of APG777;

median percent change from baseline in TARC

In addition, as shown in Figure 10 below, multiple doses of APG777 suppressed TARC with deep and sustained inhibition for approximately six months.

Figure 10 — TARC inhibition data for APG777 from our Phase 1 trial in receiving a multi-dose injection of 300mg D1, D15 of APG777

In March 2024, we reported that single doses of APG777 up to 1,200 mg and multiple doses of 300 mg were well-tolerated with a favorable safety profile consistent with the existing third-party data supporting the safety of the anti-IL-13 class.

In December 2024, we confirmed that safety data were consistent with the data reported in March 2024.

The most common treatment-emergent adverse events (“TEAEs”) were vascular access site pain, vessel puncture site bruise, headache, and vascular access bruising.

83.3% of participants observed at least one TEAE;

16.7% of participants observed at least one drug-related AE.

There were no Grade 3 TEAEs or severe adverse events related to study drug.

No AEs led to discontinuation of the study.

The last participant visit in the Phase 1 trial occurred in January 2025.

In the first quarter of 2024, we filed an IND for APG777.

In the first quarter of 2024, we also initiated a Phase 1 trial in healthy volunteers in the United States for subjects of Japanese descent and have completed dosing in that trial.

Phase 2 Trial in AD

In May 2024, we initiated APEX, a randomized, placebo-controlled, 16-week Phase 2 clinical trial of APG777 in patients with moderate-to-severe AD.

The trial is designed to combine the typical Phase 2a and 2b portions of a clinical trial into a single protocol.

A schematic of the trial design is shown in Figure 11 below.

Figure 11 — Phase 2 trial design evaluating APG777 in patients with AD

16-week topline data from Part A of the integrated Phase 2 AD trial are expected in mid-2025.

We enrolled 123 patients randomized 2:1 to APG777 and placebo with a primary endpoint of mean percentage changes in EASI score from baseline to Week 16 and secondary endpoints include EASI75 and IGA0/1 at week 16.

In February 2025, we announced that the last patient in the Part A portion of the APEX trial had been dosed and we expect 16-week topline data from Part A portion in mid-2025.

Also in February 2025, we announced that we had commenced dosing of the Part B portion of the APEX Phase 2 trial, which is a randomized, placebo-controlled dose optimization with approximately 280 patients randomized 1:1:1:1 to high, medium, or low dose APG777 and placebo with primary endpoint of mean percentage changes in EASI score from baseline to Week 16.

All patients benefiting from treatment will have the opportunity to continue to APG777 maintenance, which will evaluate three- to six-month dosing.

The integrated design is expected to provide for significant timeline acceleration by combining Phase 2a and Phase 2b elements into a single study protocol and we were able to transition from completing enrollment in Part A to enrolling Part B within one week.

We expect that Part A sites will participate in Part B, which we anticipate will avoid delays for site startup between the two parts.

Doses in the Phase 2 trial are enabled by APG777’s potentially best-in-class PK profile, extended half-life, and high-concentration formulation.

Our 180mg/mL formulation enables a 44% higher dose of APG777 compared to EBGLYSS in the same volume.

Generally, the half-life of mAbs is consistent between healthy volunteers and patients.

Consequently, we believe that the PK parameters derived from the Phase 1 trial in healthy volunteers can be used to model dosing regimens in the subsequent Phase 2 and Phase 3 trials in patients with AD and other I&I indications.

The APG777 Phase 2 induction regimen is designed to exceed EBGLYSS (lebrikizumab) exposures by approximately 30 to 40% with potential for improved clinical outcomes and maintenance regimen is designed to equal lebrikizumab’s exposures.

In third-party Phase 3 trials of lebrikizumab, approximately 30% higher exposure was seen in the low bodyweight group (less than 60 kg), which also had numerically higher efficacy than the overall study population across all key endpoints, including EASI-75 and more stringent endpoints such as EASI-90 and IGA 0/1.

APG777’s higher induction exposures are based on a planned six injection induction regimen given in the first sixteen weeks of APG777 treatment.

This is approximately half as many of the 11 injections of lebrikizumab given during the same period.

Modeling of the targeted induction exposures are shown in Figure 12 below.

Figure 12 — Modeled target induction exposures in APG777 Phase 2 trial

At 52 weeks, exposures of APG777 dosed every three or six months are designed to approximately equal those of EBGLYSS.

Expansion opportunities for APG777

IL-13 has been found to be elevated in other inflammatory conditions.

Based on our initial clinical data, we plan to advance the development of APG777 in asthma and EoE, by initiating a Phase 1b trial in asthma in the first half of 2025, followed by a Phase 2b trial in asthma in the second half of 2025, and launching a Phase 2 trial in EoE in 2026.

We believe asthma to be an important expansion opportunity for APG777 given the significant overlap with AD (31% according to third-party market research studies) and unmet need for extended dosing biologics that do not sacrifice clinical benefit.

Extended duration therapies may lead to increased adherence rates with better control and outcomes for these patients.

Eosinophilic asthma is a recognized subtype associated with increased severity and late-onset asthma.

IL-13 can induce immune activation and eosinophilic response broadly, and in the case of asthma, contribute to inflammation, airway hyperreactivity and recruitment of eosinophils to lung tissues.

Further, in third-party clinical studies, IL-13 and eosinophils have been shown to be positively correlated in airway lumen.

Thus, we believe targeting IL-13 in eosinophilic asthma is a compelling approach.

Asthma is estimated to affect 40 million adults and 12 million children in the United States, France, Germany, Italy, Japan, Spain and the United Kingdom.

Currently, the asthma market is greater than $10 billion in the seven major markets.

We plan to advance the development of APG777 in asthma by initiating a Phase 1b trial in asthma in the first half of 2025, followed by a Phase 2b trial in asthma in the second half of 2025.

We expect data from the Phase 1b trial in 2026.

Eosinophilic Esophagitis

EoE is a chronic inflammatory condition of the esophagus, with the hallmark histological finding being eosinophilic infiltrates (i.e., presences of eosinophils in the tissue).

When not treated appropriately, EoE progresses to cause scarring and strictures of the esophagus, which gives patients significant trouble with eating and drinking and potential nutritional compromise.

The only available biologic for the treatment of EoE is DUPIXENT, which was approved for this indication in 2022, and requires weekly dosing.

DUPIXENT’s approval in EoE further supports the scientific rationale for IL-13/IL-4Rα targeting agents in treating EoE.

We plan to initiate a Phase 2 trial in EoE in 2026.

Other Indications

We expect to further evaluate opportunities to develop APG777 for other I&I indications, including AA, CRSwNP, CSU, and PN.

Zumilokibart is designed to interrupt the heterodimer formation and thus disrupt IL-13 signaling as shown in Figure 7 below.

Figure 7 — Zumilokibart is designed to disrupt IL-13 signaling by preventing the formation of the IL-13Rα1-IL4Rα heterodimer

We are developing zumilokibart and APG990 together as a potential first-in-class coformulation combining deep and sustained inhibition of Type 2 inflammation via zumilokibart’s inhibition of IL-13 with broader inhibition of Type 1-3 inflammation through APG990’s inhibition of OX40L.

APG990 is an SQ extended half-life mAb targeting OX40L.

7 unchanged sentences

OX40L blockade therefore has two mechanisms by which it might have impact on the pathology associated with inflammatory conditions, first by suppressing inflammatory T cell activation, and second by increasing the proliferation of Treg cells, which can serve to further reduce effector T cell function.

Currently, there are only two mechanisms of action targeted by approved biologic agents in atopic dermatitis, IL-13 and IL-4Rα.

Targeting OX40L could represent a third mechanism of action.

OX40L, which is positioned further upstream in the inflammatory pathway than IL-13, allowing for a potentially broader impact on the inflammatory cascade by inhibiting Type 1, Type 2, and Type 3 pathways.

APG990 Development

In May 2024, we finalized the nomination of a development candidate for APG990 and in August 2024, we commenced dosing of the first participants in the Phase 1 clinical trial in healthy volunteers.

In our head-to-head preclinical assays, APG990 has demonstrated similar or improved potency to amlitelimab, an OX40L antibody candidate in late-stage clinical development.

Figure 13 below depicts a 3D rendering of human OX40L generated from our head-to-head preclinical studies.

The blue highlights the epitope, or binding site, of amlitelimab, which overlaps with APG990’s epitope, also highlighted with hatch marks.

Figure 13 — Binding site of APG990 against amlitelimab

In our head-to-head studies of APG990 and amlitelimab in NHPs, APG990 demonstrated half-life of 26 days versus 21 days for amlitelimab.

In addition, based on our preclinical studies, we believe APG990 can be dosed every three to six months in maintenance, which, if our clinical trials are successful, would represent a significant improvement compared to first generation OX40L antibodies that are expected to be dosed every four to twelve weeks.

Our APG990 Phase 1 clinical trial is designed as a double-blind, placebo-controlled, first-in-human, single-ascending dose trial designed to evaluate the safety and PK of APG990 in 40 healthy adult participants across five cohorts.

Doses of subcutaneous APG990 evaluated in the study included 75mg, 150mg, 300mg, 600mg and 1,200mg.

In March 2025, we announced data from our APG990 Phase 1 clinical trial.

APG990 interim Phase 1 pharmacokinetic (PK) data showed a half-life of approximately 60 days across doses tested, supporting the potential for testing every three- and six-month maintenance dosing with as little as 50 mg.

APG990 generally demonstrated dose proportionality and low variability.

Figure 14 below depicts the single-dose concentration-time profile from the ongoing APG990 Phase 1 trial.

Figure 14—Single-dose concentration-time profile

APG990 was well tolerated across all cohorts, with doses up to 1,200mg.

The most common (≥10%) treatment-emergent adverse events (TEAEs) were headache.

53% of participants observed at least one TEAE and there were no Grade 3 TEAEs related to study drug or severe adverse events.

No adverse events led to study discontinuation.

There have been no cases of pyrexia or chills.

Currently, there are three mechanisms of action targeted by approved biologic agents in atopic dermatitis, IL-13, IL-4Rα, and IL-31R.

Targeting OX40L could represent an additional mechanism of action.

OX40L, which is positioned further upstream in the inflammatory pathway than IL-13, may allow for a potentially broader impact on the inflammatory cascade by inhibiting Type 1, Type 2, and Type 3 pathways.

Potential clinical benefit of targeting both IL-13 and OX40L

Multiple studies have demonstrated that the upregulation of type 2 cytokines in the skin, particularly IL-13, is a key driver of inflammation in AD.

However, other pathways that are activated in AD include Type 1 (e.g., interferon-gamma [IFNγ]) and Type 3 (e.g., IL-22, IL-17) responses.

Therefore, due to the heterogeneity of inflammatory involvement in AD, we believe that blocking multiple targets, such as simultaneous inhibition of IL-13 and OX40L, could allow us to provide benefit to patients with AD and other I&I indications.

More specifically, we believe that inhibition of IL-13 with APG777 could provide depth of inhibition for the core driver of inflammation in AD, namely Type 2 inhibition, while inhibition of OX40L with APG990 could provide breadth of inhibition across a broader range of inflammatory subtypes (Types 1-3) and cytokines, but with less depth, addressing AD heterogeneity.

This dual mechanism could, therefore, improve the breadth or depth (or both) of clinical outcomes.

We have generated preclinical data to support our approach to targeting both IL-13 and OX40L.

In our preclinical ex vivo human allogeneic lymphocyte reaction assay, we demonstrated that APG279 targets all inflammatory types, including near-complete Type 2 inhibition, with the potential for every 3-month (or less frequent) dosing.

We plan to develop APG279 as a potential first-in-class coformulation for the treatment of AD combining deep and sustained inhibition of Type 2 inflammation via APG777’s inhibition of IL-13 with broader inhibition of Type 1-3 inflammation through APG990’s inhibition of OX40L.

APG279 has been shown to retain stability, injectability, and convenience of individual components.

In preclinical studies it has demonstrated broad inhibition of Type 1, Type 2 and Type 3 inflammation, similar to what was seen with JAK inhibition, but with potential for better tolerability than JAK inhibitors.

Following our positive interim results from the APG990 Phase 1 clinical trial, we believe that APG990’s PK profile supports the potential for a single 2 mL co-formulated injection of APG279 (APG777 + APG990) administered every three- and six- months in maintenance.

In addition, preclinical toxicology studies of the combination of APG777 and APG990 showed no findings at any dose level, including the highest dose tested of 150 mg/kg per agent.

Based on these results, we plan to submit an IND application or foreign equivalent for APG279.

Following clearance, we plan to initiate a Phase 1b clinical trial designed to evaluate APG279 against DUPIXENT in approximately 50 to 75 patients with moderate-to-severe AD with a readout expected in the second half of 2026.

APG279 will be co-administered in the proof-of-concept Phase 1b trial with coformulation planned for future clinical studies.

In preclinical studies, the combination of APG279 has been shown to drive closer to JAK-like inhibition of Type 1, 2, and 3 signaling compared to approved or in-development biologics, with the potential for best-in-class dosing and better tolerability in AD and a variety of other I&I diseases.

We are currently testing the clinical benefit of APG279 as a coformulation in the Phase 1b trial of APG279 against DUPIXENT in patients with moderate-to-severe AD.

We are developing zumilokibart and APG333 together as APG273, a potential quarterly or less frequently dosed co-formulation for the treatment of asthma and COPD.

APG333 is a fully-human mAb against TSLP.

TSLP is an epithelial cell-derived cytokine that has emerged as an attractive validated target for the treatment of people living with asthma and COPD, with the potential for extended half-life and to be used in combination with other mAbs for potentially greater efficacy in broader populations.

TSLP is an epithelial cell-derived cytokine that has emerged as an attractive validated target for the treatment of people living with asthma and COPD.

APG333 has the potential to be used in combination with other mAbs for potentially greater efficacy in broader populations.

TSLP is a cytokine belonging to the alarmin family that is involved in the activation and modulation of the immune system.

TSLP is primarily produced by epithelial cells in response to tissue damage by a variety of agents (allergens, viruses, bacteria, etc.) and functions as a potent immune activator by agonizing a heterodimeric complex composed of the TSLPR and IL-7Ra.

Formation of the TSLP-TSLPR-IL7Rα heterocomplex activates downstream signaling pathways that regulate a wide array of immune functions, including epithelial barrier dysfunction, dendritic cell activation, and type 2 ILC2s activation/survival.

TSLP signaling also drives the recruitment of immune cells, the induction of Th2 responses, and the regulation of B cell function, explaining its involvement in tissue homeostasis, host defense, and the pathophysiology of allergic and inflammatory diseases including asthma and COPD.

TSLP plays important roles in Type 2 and Type 3 inflammation and TSLP inhibition has shown clinical benefit in both eosinophilic and non-eosinophilic asthma.

TSLP inhibition has been clinically validated, with the only approved product on the market for the treatment of severe asthma without biomarker or phenotype restrictions.

APG333 has similar binding as a first generation mAb, TEZSPIRE, for TSLP across our head-to-head preclinical assays.

Figure 15 below depicts a 3D rendering of human TSLP generated from our head-to-head preclinical studies.

The gray highlights the epitope, or binding site, of TEZSPIRE, which overlaps with APG333’s epitope, also highlighted with blue hatch marks.

Additionally, in our head-to-head studies of APG333 and TEZSPIRE in NHPs, APG333 showed a significantly longer half-life than TEZSPIRE.

In these preclinical studies, APG333’s half-life was 24 days, as compared to 11 days for TEZSPIRE.

Based on these preclinical studies, we believe that the longer half-life could support dosing every three to six months in the clinic.

Figure 15 — Binding site of APG333 against tezepelumab (TEZSPIRE)

APG333 Development

In October 2024, we finalized the nomination of a development candidate for APG333 and in December 2024 we initiated a Phase 1 clinical trial of APG333 in healthy volunteers.

The APG333 Phase 1 clinical trial is designed as a double-blind, placebo controlled, first-in-human, SAD trial in healthy volunteers.

The study will evaluate the safety, tolerability and pharmacokinetics of APG333 and is expected to enroll approximately 32 healthy adults into four cohorts.

We expect interim data from the APG333 Phase 1 trial in the second half of 2025.

Currently, other mechanisms targeted by approved biologic agents in asthma include IL-4Ra, IL-5, IL-5R and IgE.

Mechanisms of approved biologic agents in COPD are IL-4Ra and IL-5.

Potential clinical benefit of targeting both IL-13 and TSLP

In preclinical studies, the combination of APG777 and APG333 has been shown to drive both inhibition of inflammation centrally and local airway responses compared to approved or in-development biologics, which only target central or local inflammation, with the potential for a significantly less frequent dosing schedule.

In our preclinical studies, we showed that APG777 activates bronchial smooth muscle cells that promote local airway responses to inflammation while APG333 targeted inflammation centrally and more broadly, showing inhibition of both Type 2 and non-Type 2 cytokines.

We believe targeting both central and local inflammation for respiratory diseases has the potential to improve clinical outcomes for patients.

We plan to evaluate APG777 and APG333 monotherapies in respective Phase 1b trials in patients with asthma in 2025 to support advancement into future combination trials in asthma and COPD.

Subject to positive data, we plan to study APG777 in combination with APG333 to drive potential best-in-class efficacy in respiratory conditions.

In preclinical studies, the combination of zumilokibart and APG333 has been shown to drive both inhibition of inflammation centrally and local airway responses compared to approved or in-development biologics, which only target central or local inflammation, with the potential for a significantly less frequent dosing schedule.

APG808 is an SQ extended half-life mAb targeting IL-4Rα, a target with clinical validation across eight different Type 2 allergic diseases.

Based on our head-to-head preclinical studies of APG808, we have demonstrated the potential to increase the half-life of IL-4Rα-targeting mAbs using half-life extension modifications.

In our head-to-head studies of APG808 and DUPIXENT in NHPs, APG808 demonstrated half-life of 27 days versus 11 days for DUPIXENT.

Moreover, in our head-to-head preclinical assay, APG808 demonstrated equivalent potency of IL-4Rα inhibition compared to DUPIXENT in a head-to-head in vitro assay.

In March 2024, we initiated a Phase 1 clinical trial of APG808 in healthy volunteers and announced positive interim safety, PK and PD data from the Phase 1 trial in December 2024 demonstrating a potential best-in-class PK

profile, including a half-life of approximately 55 days, supporting the potential for every two- to three-month maintenance dosing.

IL-4Rα is a known driver of disease pathology in I&I indications

APG808’s target, IL-4Rα, is a known driver of pathogenesis for a number of diseases.

By blocking IL-4Rα, we believe APG808 will prevent formation of the IL-13Rα1-IL-4Rα heterodimer, which is understood to be a key pathogenic step in multiple Th2-driven diseases such as AD, asthma, COPD and CRSwNP.

Preventing the formation of the IL-13Rα1-IL-4Rα heterodimer in turn prevents recruitment of members of the JAK family of enzymes and prevents the signaling cascade that results in the expression of pro-inflammatory cytokines and leads to an immune response by the body in these diseases.

APG808 has demonstrated equivalent potency to DUPIXENT in head-to-head in vitro assays

APG808 was engineered to demonstrate similar preclinical activity to available therapies in our head-to-head studies.

Specifically, an assay was performed to measure downstream functional inhibition of the IL-13/IL-4 pathway, meaning after IL-13Rα1 and IL-4Rα heterodimerization.

Measuring downstream functional inhibition of the pathway is critical, as this measures the mAb’s impact on the inflammatory cascade that causes the features, signs, and symptoms associated with I&I indications.

In our head-to-head preclinical study, DUPIXENT and APG808 showed similar binding, with femtomolar affinity for IL-4Rα, and similar inhibition across the three in vitro assays which measure downstream functional inhibition of the IL-13/IL-4 pathway (pSTAT6 induction, inhibition of TF-1 proliferation, and inhibition of TARC secretion).

Figure 16 below depicts a 3D rendering of human IL-4Rα generated from our head-to-head preclinical studies.

The gray highlights the epitope, or binding site, of dupilumab (DUPIXENT), which overlaps with APG808’s epitope, also highlighted with hatch marks.

Figure 16 — APG808's epitope on IL-4Rα overlaps with dupilumab and leverages proven mechanism of action and biology

APG808 Dosing

In our head-to-head preclinical studies of APG808 and DUPIXENT in NHPs, APG808 showed a significantly longer half-life than DUPIXENT.

In these preclinical studies, APG808’s half-life was up to 27 days, as compared to 11 days for DUPIXENT.

APG808 Development

In March 2024, we commenced dosing of the first healthy volunteers in the APG808 Phase 1 trial and in September 2024, we commenced dosing of the first asthma patients as a cohort in that Phase 1 trial.

The APG808 Phase 1 trial was designed as a double-blind, placebo-controlled study in healthy volunteers with single ascending doses.

The APG808 Phase 1 trial enrolled 32 healthy adult participants into four SAD cohorts.

In December 2024, we shared positive interim safety, PK and PD data from the Phase 1 trial.

APG808 demonstrated a potential best-in-class PK profile, including a half-life of approximately 55 days, supporting the potential for every two- to three- month maintenance dosing.

Single doses of APG808 demonstrated a deep and sustained effect on PD markers out to approximately three months (longest follow-up available at time of data cut).

APG808 was well-tolerated across all dose groups.

We are also now evaluating APG808 in a Phase 1b trial in patients with asthma, with data expected in the first half of 2025.

Expansion opportunities for APG808

IL-4Rα biology has been implicated in a number of different indications, including AD, asthma, COPD, CRSwNP, EoE, PN and CSU.

We intend to evaluate additional expansion opportunities in one or more of such indications.

We believe that APG808 could potentially benefit patients with eosinophilic asthma.

DUPIXENT, which also targets IL-4Rα but is dosed every other week, is approved in asthma in patients six years of age or older with moderate-to-severe-asthma with eosinophilic phenotype or oral corticosteroids dependent regardless of phenotype and has shown a 46% reduction in the rate of annualized exacerbations in pivotal studies, which we believe validates targeting IL-4Rα as an approach to treating asthma.

Additional Expansion Opportunities

We believe that each of our programs has the potential to impact multiple additional I&I indications beyond AD and COPD, including asthma and EoE as well as AA, CRSwNP, CSU, and PN.

Based on third-party claims data, 31% of AD patients also carry an asthma diagnosis.

Based on feedback from dermatologists, we believe that there is significant value in having both indications on a label because of this overlap.

Asthma is estimated to affect 40 million adults and 12 million children in the United States, France, Germany, Italy, Japan, Spain and the United Kingdom.

We do not yet have clinical data showing the ability of our programs to treat other indications and there can be no assurance that our programs will have similar or comparable results to any products or later-stage product candidates for these indications.

Alopecia Areata

Patients with AA represent a population with high unmet need, given there are no approved targeted biologic therapies.

Recent third-party Phase 2a data for DUPIXENT demonstrated clinical benefit in patients with AA, which we believe provides support for the IL-4/IL-13 pathway blockade as a potential treatment for AA.

Chronic Rhinosinusitis with Nasal Polyps

CRSwNP is commonly comorbid with asthma and the two diseases have overlapping biology.

IL-4 and IL-13 have been shown to play important roles in the pathophysiology of CRSwNP.

Further, DUPIXENT is approved for this indication, which we believe demonstrates the potential for IL-13 and/or IL-4Rα targeting.

Chronic Spontaneous Urticaria

CSU is a disease where mast cells are believed to be the key effector cells, although data has also demonstrated that IL-4 and IL-13 may be key in the development and maintenance of CSU.

Further, we believe the positive Phase 3 data for DUPIXENT in patients with CSU that is not adequately controlled with the current standard of care suggests the role of the IL-4/IL-13 heterodimer signaling complex’s involvement in CSU.

Prurigo Nodularis

PN is a chronic inflammatory condition of the skin where lesions have shown Th2-associated cytokines such as IL-4, IL-13 and IL-31.

DUPIXENT is approved for this indication, which we believe demonstrates the potential for IL-13 and/or IL-4Rα targeting.

Additional I&I Indications

We may expand into additional I&I indications, such as Crohn disease, lupus, rheumatoid arthritis, psoriasis and ulcerative colitis, that are implicated in the disease pathways targeted by our current or future programs.

Our Collaboration, License and Services Agreements

3 unchanged sentences

The 2022 Option Agreement initially included two selected targets, IL-13 and IL-4Rα, and was subsequently amended in November 2022 to include an additional selected target, OX40L.

Under the 2022 Option Agreement, we have the exclusive option to, on a research program-by-research program basis, be granted an exclusive, worldwide license to all of Paragon’s right, title and interest in and to the intellectual property resulting from the applicable research program to develop, manufacture and commercialize the antibodies and products directed to the selected targets (each, an “Option”).

2022 Option Agreement, we have the exclusive option to, on a research program-by-research program basis, be granted an exclusive, worldwide license to all of Paragon’s right, title and interest in and to the intellectual property resulting from the applicable research program to develop, manufacture and commercialize the antibodies and products directed to the selected targets (each, an “Option”).

From time to time, we can choose to add additional targets to the collaboration by mutual agreement with Paragon.

7 unchanged sentences

In consideration for the exclusive options granted under the 2022 Option Agreement, we paid an upfront cash amount of $1.3 million and issued 1,250,000 common units to Paragon.

Paragon was also entitled to up to an additional 3,750,000 of common units in exchange for the rights granted under the 2022 Option Agreement, which were issued in connection with the closings of the additional tranches of the Series A Preferred Unit financing.

Under the 2022 Option Agreement, on a Research Program-by-Research Program basis following the finalization of the Research Plan for each respective Research Program, we are required to pay Paragon a nonrefundable fee in cash of $0.5 million.

8 unchanged sentences

For each Research Program, the parties must establish a Research Plan.

In January 2024, we agreed on an initial Research Plan with Paragon that outlines the services that will be performed commencing at inception of the arrangement related to TSLP.

In January 2024, we agreed on an initial Research Plan with Paragon that outlined the services that would be performed commencing at inception of the arrangement related to TSLP.

Our exclusive option with respect to each Research Program is exercisable at our sole discretion at any time during the period beginning on the initiation of activities under the associated Research Program and ending a specified number of days following the delivery of the data package from Paragon related to the results of the Research Plan activities.

17 unchanged sentences

In August 2024, we exercised our option available under the 2023 Option Agreement with respect to the TSLP Research Program and entered into the associated license agreement (the “TSLP License Agreement,” and collectively with the IL-13 License Agreement, the IL-4Rα License Agreement and the OX40L License Agreement, the “License Agreements”).

Under the terms of the License Agreements, Paragon granted to us an exclusive, worldwide, royalty-bearing, sublicensable right and license with respect to certain information, patent rights and sequence information related to antibodies directed at the respective target to use, make, sell, import, export and otherwise exploit the antibodies

directed at the respective target.

Pursuant to the License Agreements, we granted to Paragon a similar license (except that such license we granted to Paragon is non-exclusive) to the respective licenses with respect to multispecific antibodies that are directed at the respective targets and one or more other antibodies.

4 unchanged sentences

Upon execution of the IL-13 License Agreement, we paid Paragon a $1.0 million fee for the nomination of a development candidate.

In August 2023, we announced the dosing of our first participants in the Phase 1 trial of APG777 and made a milestone payment of $2.0 million in the fourth quarter of 2023.

In August 2023, we announced the dosing of our first participant in the Phase 1 trial of zumilokibart (APG777) and made a milestone payment of $2.0 million in the fourth quarter of 2023.

In November 2023, we finalized the nomination of a development candidate under the IL-4Rα License Agreement and made a milestone payment of $1.0 million to Paragon in the fourth quarter of 2023.

In March 2024, we announced the dosing of our first participants in a Phase 1 trial of APG808 and made a milestone payment of $2.0 million to Paragon in the first quarter of 2024.

In March 2024, we announced the dosing of our first participant in a Phase 1 trial of APG808 and made a milestone payment of $2.0 million to Paragon in the first quarter of 2024.

In May 2024, we finalized the nomination of a development candidate under the OX40L License Agreement and made a milestone payment of $1.0 million to Paragon in the second quarter of 2024.

In August 2024, we announced the dosing of our first participants in the Phase 1 trial of APG990 and made a milestone payment of $2.0 million in the third quarter of 2024.

In August 2024, we announced the dosing of our first participant in the Phase 1 trial of APG990 and made a milestone payment of $2.0 million in the third quarter of 2024.

In October 2024, we finalized the nomination of a development candidate under the TSLP License Agreement and made a milestone payment of $3.0 million to Paragon in the fourth quarter of 2024.

2 unchanged sentences

Royalties are due on a product-by-product and country-by-country basis beginning upon the first commercial sale of each product and ending on the later of (i) 12 years after the first commercial sale of such product in such country and (ii) expiration of the last valid claim of a patent covering such product in such country.

Unless earlier terminated, the License Agreements remain in effect until the expiration of the last-to-expire Royalty Term for any and all products associated with the respective license.

We may terminate the agreement in its entirety or on a country-by-country or product-by-product at any time for any or no reason upon 60 days’ advance written notice to Paragon, and either party may terminate for (i) the other party’s material breach that remains uncured for 90 days (or 30 days with respect to any failure to make payments) following notice of such breach and (ii) the other party’s bankruptcy.

Upon any termination prior to the expiration of a License Agreement, all licenses and rights granted pursuant to such License Agreement will automatically terminate and revert to the granting party and all other rights and obligations of the parties will terminate.

Biologics Master Services Agreement — WuXi Biologics (Hong Kong) Limited

In June 2022, Paragon and WuXi Biologics (Hong Kong) Limited (“WuXi Biologics”) entered into a biologics master services agreement (the “WuXi Biologics MSA”), which was subsequently novated to us by Paragon in the second quarter of 2023.

The WuXi Biologics MSA governs all development activities and GMP manufacturing and testing for our APG777, APG990, APG333 and APG808 programs, as well as potential future programs, on a work order basis.

The WuXi Biologics MSA governs all development activities and GMP manufacturing and testing for zumilokibart (APG777), APG990, APG333 and APG808, as well as potential future product candidates, on a work order basis.

Under the WuXi Biologics MSA, we are obligated to pay WuXi Biologics a service fee and all non-cancellable obligations in the amount specified in each work order associated with the agreement for the provision of services.

6 unchanged sentences

Under the Cell Line License Agreement, we received a non-exclusive, worldwide, sublicensable license to certain of WuXi Biologics’ know-how, cell line, biological materials (the “WuXi Biologics Licensed Technology”) and media and feeds to make, have made, use, sell and import certain therapeutic products produced through the use of the cell line licensed by WuXi Biologics under the Cell Line License Agreement (the “WuXi Biologics Licensed Products”).

Specifically, the WuXi Biologics Licensed Technology is used to manufacture a component of the APG777, APG990, APG333 and APG808 programs.

Specifically, the WuXi Biologics Licensed Technology is used to manufacture zumilokibart (APG777), APG990, APG333 and APG808.

In consideration for the license, we have paid WuXi Biologics a non-refundable license fee of $150,000.

2 unchanged sentences

The Cell Line License Agreement will continue indefinitely unless terminated (i) by us upon six months’ prior written notice and our payment of all undisputed amounts due to WuXi Biologics through the effective date of termination, (ii) by WuXi Biologics for a material breach by us that remains uncured for 60 days after written notice, (iii) by WuXi Biologics if we fail to make a payment and such failure continues for 30 days after receiving notice of such failure, or (iv) by either party upon the other party’s bankruptcy.

Master Services Agreement and Project Specific Agreements — Samsung Biologics Limited

In March 2025, we entered into a Master Services Agreement (the “Samsung Biologics MSA”), made effective as of February 28, 2025, with Samsung Biologics Co., Ltd.

(“Samsung Biologics”), pursuant to which Samsung Biologics will manufacture and supply us with zumilokibart (APG777) drug substance (the “Samsung Biologics Product”) for clinical development and commercial sale, if approved.

We are obligated to pay Samsung Biologics service fees for each manufactured batch, as well as the costs of materials purchased by Samsung Biologics and expenses including testing and storage, which such costs and fees will be specified in Project Specific Agreements (each a “PSA”).

Also in March 2025, we entered into a PSA (the “Initial PSA”) with Samsung Biologics, made effective as of February 28, 2025, pursuant to which Samsung Biologics will produce clinical batches of the Samsung Biologics Product at its facility in Incheon, South Korea, perform process characterization and validation, and manufacture process performance qualification lots of the Samsung Biologics Product.

Under the Initial PSA, we must purchase certain minimum quantities of the Samsung Biologics Product and have agreed to pay Samsung Biologics as determined pursuant to the terms of the Initial PSA.

The Samsung Biologics MSA will terminate in February 2035, or, if a PSA is still in effect, when such PSA terminates, and may be extended upon mutual agreement of the parties.

The Initial PSA will terminate in December 2034.

We or Samsung Biologics may terminate the Samsung Biologics MSA or the Initial PSA in the event of an uncured material breach by, insolvency of or inability to perform due to a force majeure event by the other party.

In the event all applicable PSAs have been terminated, Samsung Biologics has agreed to provide assistance with certain technology transfer matters, subject to exceptions.

If we terminate the Samsung Biologics MSA or Initial PSA without cause, we will generally be responsible for paying the purchase price for our aggregate product commitment for the remainder of the term, less any amounts we have already paid.

In February 2026, the Company entered into a separate PSA with Samsung that would provide for the commercial manufacture of zumilokibart drug substance should the program eventually receive regulatory approval.

If specific circumstances render Apogee unable to proceed with commercial distribution, the PSA provides for Samsung to receive compensation, including for contractually obligated expenses, and an exit fee in the high single-digit millions.

For additional detail regarding the agreements described above, see the section titled “Notes to Consolidated Financial Statements—Other Significant Agreements” included elsewhere in this Annual Report.

The biotechnology and biopharmaceutical industries are characterized by continuing technological advancement and significant competition.

While we believe that our programs, technology, development experience and scientific knowledge provide us with competitive advantages, we face competition from major pharmaceutical and biotechnology companies, academic institutions, governmental agencies and public and private research institutions, among others.

While we believe that our product candidates, technology, development experience and scientific knowledge provide us with competitive advantages, we face competition from major pharmaceutical and biotechnology companies, academic institutions, governmental agencies and public and private research institutions, among others.

Any product candidates that we successfully develop and commercialize will compete with existing therapies and new therapies that may become available in the future.

2 unchanged sentences

Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies.

These competitors also compete with us in recruiting and retaining qualified scientific, clinical and management personnel, establishing clinical trial sites, patient enrollment for clinical trials as well as in acquiring technologies complementary to, or necessary for, our programs.

These competitors also compete with us in recruiting and retaining qualified scientific, clinical and management personnel, establishing clinical trial sites, patient

enrollment for clinical trials as well as in acquiring technologies complementary to, or necessary for, our programs.

Key competitive factors affecting the success of all our product candidates that we develop, if approved, are likely to be efficacy, safety, convenience, presentation, price, the level of generic competition and the availability of reimbursement from government and other third-party payors.

Our competitors may also obtain FDA or other regulatory approval for their products more rapidly than we may obtain approval for ours, which could result in our competitors establishing a strong market position before we are able to enter the market.

Specifically, there are several companies, including major pharmaceutical companies, developing or marketing treatments that may be approved for the same indications and/or disease as our programs.

We do not yet have clinical data for any of our programs and there can be no assurance that our programs will have similar or comparable results.

Specifically, there are several companies, including major pharmaceutical companies, developing or marketing treatments that may be approved for the same indications and/or disease as our product candidates.

We are early in the clinical development stage of our product candidates and there can be no assurance that our product candidates will have similar or comparable results.

Over time, I&I markets have developed with a general increasing number of competitors, improved efficacy and improved dosing intervals (i.e.

11 unchanged sentences

There are several approved treatments that target JAK1 and/or JAK2 to treat AD, including abrocitinib, marketed as CIBINQO by Pfizer, and upadacitinib, marketed as RINVOQ by AbbVie.

Change in EASI score at 16 weeks is a common endpoint in AD.

For example, the percentage of patients achieving EASI 75 on a placebo-adjusted basis in Phase 2 and average of Phase 3 monotherapy trials in AD were 59% and 62%, respectively, for upadacitinib at 30mg dosed daily, 42% and 51%, respectively, for upadacitinib at 15mg dosed daily, 36% and 38%, respectively, for lebrikizumab at 250mg dosed every two weeks, 40% and 34%, respectively, for DUPIXENT at 300mg dosed every two weeks, 49% and 51%, respectively, for abrocitinib at 200mg dosed daily, and 25% and 21%, respectively, for abrocitinib at 100mg dosed daily.

With respect to biologics with global Phase 3 data in AD, DUPIXENT, EBGLYSS, ADBRY, and NEMLUVIO have all demonstrated statistically significant results.

In two Phase 3 trials of DUPIXENT dosed every two weeks in patients with AD, at 16 weeks, DUPIXENT showed 38.0% and 36.1% of treated patients achieved IGA 0/1 compared to 10.3% and 8.5% on placebo, respectively.

Further, 51.3% and 44.2% of patients treated with DUPIXENT achieved EASI‑75, compared to 14.7% and 11.9% on placebo, respectively.

All differences were statistically significant.

Of the 16‑week responders who received DUPIXENT every two weeks during the induction period, 44% of patients dosed every four weeks and 54% of patients dosed every two weeks in the maintenance period achieved IGA 0/1 and 58% of patients dosed every four weeks and 72% of patients dosed every two weeks in the maintenance period achieved EASI‑75 at 52 weeks.

In two Phase 3 trials of EBGLYSS dosed every two weeks in patients with AD, at 16 weeks, EBGLYSS showed 43.1% and 33.2% of treated patients achieved IGA 0/1 compared to 12.7% and 10.8% on placebo, respectively.

Further, 58.8% and 52.1% of patients treated with EBGLYSS achieved EASI‑75, compared to 16.2% and 18.1% of patients on placebo, respectively.

All differences were statistically significant.

Of the 16-week responders who received EBGLYSS every two weeks during the induction period, 78% of patients dosed every four weeks and 71% of patients dosed every two weeks in the maintenance period achieved IGA 0/1 and 82% of patients dosed every four weeks and 78% of patients dosed every two weeks in the maintenance period achieved EASI‑75 at 52 weeks.

In two Phase 3 trials of ADBRY dosed every two weeks in patients with AD, at 16 weeks, ADBRY showed 15.8% and 22.2% of treated patients achieved IGA 0/1 compared to 7.1% and 10.9% on placebo, respectively.

Further, 25.0% and 33.2% of patients treated with ADBRY achieved EASI‑75, compared to 12.7% and 11.4% of patients on placebo, respectively.

All differences were statistically significant.

In two Phase 3 trials with topical corticosteroids and topical calcineurin inhibitors, NEMLUVIO dosed every four weeks in patients with AD, showed 35.6% and 37.7% IGA 0/1 compared to 24.6% and 26.0% in the placebo group.

For EASI-75, 43.5% and 42.1% of treated patients achieved the endpoint compared to 29.0% and 30.2% in the placebo group.

All differences were statistically significant.

We do not yet have clinical data in patients with AD for our programs and there can be no assurance that our programs will have similar or comparable results.

We are also aware of several product candidates in clinical development for AD.

Amlitelimab is an OX40L mAb, which is currently being evaluated in a Phase 3 trial by Sanofi and has demonstrated EASI-75 of 61.5% compared to 29.4% in the placebo group at week 16 when dosed every four weeks at 250mg with a 500mg loading dose (LD) in a Phase 2b trial.

22.1% of patients treated with amlitelimab 250mg with LD achieved IGA0/1 at Week 16 compared to 5.1% of placebo patients.

Rocatinlimab is an OX40 mAb, which is currently being evaluated in a Phase 3 trial by Amgen and Kyowa Kirin Co., Ltd.

and has demonstrated EASI-75 of 54% compared to 11% for placebo in a Phase 2 trial.

The first Phase 3 trial showed EASI-75 of 32.8% compared to 13.7% placebo at week 24.

For IGA 0/1, 19.3% of treated patients achieved the endpoint versus 6.6% in the placebo group.

Other agents include rezpegaldesleukin, a rIL-2 in Phase 2 trials by NEKTAR, temptokibart, an IL-22R in Phase 2 trials by LEO Pharma, GSK1070806, an IL-18 in Phase 2 trials by GSK, and KT-621, an oral STAT6 degrader in Phase 1 trials, by Kymera.

We are also aware of several product candidates in clinical development for AD, including but not limited to:

Amlitelimab, an OX40L mAb, by Sanofi;

and rocatinlimab, a T-cell rebalancing mAb that targets the OX40 receptor, by Kyowa Kirin Co., Ltd.;

rezpegaldesleukin, an anti-IL-2, by NEKTAR;

temptokibart, an anti-IL-22R, by LEO Pharma;

KT-621, an oral STAT6 degrader, by Kymera;

GHZ339, an anti-IL-13/IL-18, by Novartis;

EVO756, an MRGPRX2 inhibitor, by Evommune;

PF-08049820, a STAT6 inhibitor, by Pfizer;

lunsekimig, an anti-IL-13/TSLP nanobody, by Sanofi;

IMG-007, an anti-OX40, by InmageneBio;

and galvokimig an anti-IL-13/IL-17AF, by UCB;

EVO301, an anti-IL-18 fusion protein, by Evommune;

camoteskimab, an anti-IL-18, by Apollo;

donzakimig, an anti-IL-13/IL-22, by UCB.

Advanced therapy penetration in AD is currently expected to ramp up from 8% in 2022 to approximately 25% by 2032.

With more convenient and patient-friendly dosing, and potentially better efficacy, we believe that the market for future penetration of biologics could expand even beyond the projected 25%.

There are several approved products for COPD, including DUPIXENT and OHTUVAYRE (ensifentrine), a PDE3/PDE4 inhibitor marketed as OHTUVAYRE by Verona Pharma.

We are aware of several other biologics in development, including mepolizumab, an IL-5 mAb from GSK which met its primary endpoint in a Phase 3 trial, itepekimab, an IL-33 mAb from Sanofi/Regeneron, which is currently being evaluated in a Phase 3 trial;

tozorakimab, an IL-33 mAb from AstraZeneca, which is currently being evaluated in Phase 3 trials;

benralizumab, an IL-5R mAb, from AstraZeneca, which is currently being evaluated in a Phase 3 trial;

tezepelumab, a TSLP mAb from AstraZeneca/Amgen, which is expected to begin a Phase 3 trial;

astegolimab, an ST2 mAb from Roche, which is currently being evaluated in Phase 2/3 trials;

and depemokimab, an IL-5 mAb from GSK, which is expected to begin Phase 3 trials.

There are several approved products for the treatment of asthma, including dupilumab, an IL-4Rα mAb marketed as DUPIXENT by Sanofi/Regeneron, omalizumab, an anti-IgE mAb marketed as XOLAIR by Genentech/Novartis, mepolizumab, an anti-IL-5 mAb marketed as NUCALA by GSK, reslizumab, an anti-IL-5 mAb marketed as CINQAIR by Teva, benralizumab, an anti-IL-5Rα mAb marketed as FASENRA by AstraZeneca,

tezepelumab, an anti-TSLP mAb marketed as TEZSPIRE by Amgen/AstraZeneca, and depemokimab, an anti-IL-5 mAb marketed as EXDENSUR by GSK.

We are also aware of several product candidates in clinical development for asthma, including but not limited to:

GB-0895, a TSLP mAb, by Generate Bio;

Lunsekimig, a IL-13/TSLP nanobody, by Sanofi, PF-07275315, an anti-IL-4/IL-13/TSLP multispecific, by Pfizer, amlitelimab, an anti-OX40L mAb, by Sanofi, verekitug, an anti-TSLPR mAb, by Upstream Bio, rocatinlimab, an anti-OX40 mAb, by Amgen, BEL512, an anti-IL-13/TSLP bispecific, by Bellenos Bio, WIN378, an anti-TSLP mAb, by Winward Bio, solrikitug, a anti-TSLP mAb, by Uniquity, KT-621, an oral STAT6 degrader, by Kymera Therapeutics, rademikibart, an anti-IL-4Rα mAb, by Connect Bio, atuliflapon, an oral FLAP inhibitor, by AstraZeneca, povorcitinib, an oral JAK1 inhibitor, by Incyte.

The only available biologic for the treatment of EoE is DUPIXENT.

There are several approved products for COPD, including DUPIXENT, NUCALA and OHTUVAYRE (ensifentrine), a PDE3/PDE4 inhibitor from Verona Pharma.

We are aware of several other biologics in development that are implicated in the disease pathways targeted by our current product candidates, including but not limited to:

mepolizumab, an anti-IL-5 mAb from GSK;

itepekimab, an anti-IL-33 mAb from Sanofi/Regeneron;

tozorakimab, an anti-IL-33 mAb from AstraZeneca;

benralizumab, an anti-IL-5R mAb, from AstraZeneca;

tezepelumab, a anti-TSLP mAb from AstraZeneca/Amgen;

and astegolimab, an anti-ST2 mAb from Roche.

Manufacturing and Supply

1 unchanged sentence

All of our preclinical and clinical drug supply development, manufacturing, storage, distribution and testing are outsourced to third-party manufacturers and facilities.

Our manufacturing strategy enables us to more efficiently direct financial resources to the research, development and commercialization of programs rather than diverting resources to internally develop and maintain manufacturing facilities.

As our programs advance through development, we expect to enter into longer-term commercial supply agreements with key suppliers and manufacturers to fulfill and secure our supply needs.

Our manufacturing strategy enables us to more efficiently direct financial resources to the research, development, and commercialization of our product candidates rather than diverting resources to internally develop and maintain manufacturing facilities.

As our product candidates advance through development, we expect to enter into longer-term commercial supply agreements with key suppliers and manufacturers to fulfill and secure our supply needs.

With our contract development and manufacturing organizations, we have developed, or expect to develop, high yield, industry standard mAb drug manufacturing processes suitable for preclinical supply, as well as clinical and commercial scale manufacturing.

We expect to use industry standard sterile liquid drug product manufacturing processes and to develop formulations and presentations that enable SQ delivery of all of our planned clinical development candidates.

APG777 drug substance and drug product have been successfully manufactured at clinical scale with acceptable yields for near-term, planned clinical trials.

Our formulation for APG777 is suitable for SQ injection.

By the time of commercialization, we expect APG777 to be administrated via a pre-filled syringe and/or autoinjector.

We use a similar approach to development and supply for our APG990, APG333 and APG808 programs.

APG990, APG333 and APG808 drug substance and drug product have been successfully manufactured at clinical scale with acceptable yields for use in our initial planned clinical trials.

While we expect to continue to devote significant resources to process development, scale-up, manufacturing resupply and registration-enabling validation activities for APG777, we believe the manufacturing processes for mAbs such as APG777 are well established and should not create meaningful impediments to either clinical development or commercial launch.

We have developed, or expect to develop, industry standard sterile liquid drug product formulations, presentations, and manufacturing processes to enable SQ delivery of all of our planned clinical development candidates.

We have successfully manufactured zumilokibart (APG777) drug substance at commercial scale for clinical trial use, and we have successfully manufactured zumilokibart drug product at clinical scale with acceptable yields for near-term, planned clinical trials.

Our formulation for zumilokibart is suitable for SQ injection.

By the time of commercialization, we expect zumilokibart to be administered via a pre-filled syringe and/or autoinjector.

We use a similar approach to the development and supply for the following product candidates:

APG990 (as a combination partner with zumilokibart for APG279), APG333 (as a combination partner with zumilokibart for APG273), and APG808.

APG990, APG333, and APG808 drug substance and drug product have been successfully manufactured at clinical scale with acceptable yields for use in our planned clinical trials.

While we expect to continue to devote significant resources to process development, scale-up, manufacturing resupply and registration-enabling validation activities for zumilokibart, we believe the manufacturing processes for mAbs such as zumilokibart are well established and should not create meaningful impediments to either clinical development or commercial launch.

We have created redundancy in our clinical supply by contracting with second source drug substance and drug product manufacturers.

However, we will continue to identify additional drug substance and drug product contract manufacturers to ensure that we will have sufficient capacity as well as redundancy within our supply chain to avoid product shortages in the future.

We currently have two sources for our preclinical and clinical supply of zumilokibart drug substance and drug product, and have entered into agreement for the commercial supply

of zumilokibart drug substance should the product candidate eventually receive regulatory approval, and we are working to finalize the terms of our potential commercial supply arrangement for zumilokibart drug product.

We have a sole source relationship for our preclinical and clinical supply of APG990 (as a combination partner with zumilokibart for APG279), APG333 (as a combination partner with zumilokibart for APG273), and APG808 drug substance and drug product.

We will continue to identify additional drug substance and drug product contract manufacturers to ensure that we will have sufficient capacity as well as redundancy within our supply chain to avoid product shortages in the future due to geopolitical uncertainties and other risks.

We will also continue to invest in development activities to ensure an acceptable cost of goods.

We will also continue to apply mitigation strategies to ensure minimal disruption to our manufacturing supply due to any future global raw material supply chain shortages.

We believe there are multiple sources for the raw materials required for the manufacture of our programs.

While any reduction or halt in the supply of raw materials, drug substance or drug product could limit our ability to develop our programs until a replacement supplier or contract manufacturer is found and qualified, we believe that we have or will be able to manufacture sufficient clinical supply of APG777, APG990, APG333 and APG808, as well as future pipeline products, to support our planned clinical trials, and have access to sufficient manufacturing capacity to support our planned clinical development program.

In light of the recently introduced BIOSECURE Act, which would prohibit federal agencies from entering into procurement contracts with an entity that uses biotechnology equipment or services from a biotechnology company of concern, we continue to take risk mitigation measures to reduce our supply chain risk in the event that WuXi Biologics or one of our other manufacturers or other supply chain vendors is impacted.

Although the BIOSECURE Act did not become law in 2024, it may be proposed again in 2025 and we have secured second source drug product manufacturing in the U.S.

and have entered into an agreement with Samsung Biologics for drug substance supply.

We intend to continue to identify and select additional source suppliers, including those based in the U.S.

We believe there are multiple sources for the raw materials required for the manufacture of our product candidates.

While any reduction or halt in the supply of raw materials, drug substance or drug product could limit our ability to develop our product candidates until a replacement supplier or contract manufacturer is found and qualified, we believe that we have or will be able to manufacture sufficient clinical supply of zumilokibart, APG990 (as a combination partner with zumilokibart for APG279), APG333 (as a combination partner with zumilokibart for APG273), and APG808, as well as future pipeline products, to support our planned clinical trials, and have access to sufficient manufacturing capacity to support our planned clinical development program.

In light of the BIOSECURE Act, which prohibits federal agencies from entering into procurement contracts with an entity that uses biotechnology equipment or services from a biotechnology company of concern, we continue to take risk mitigation measures to reduce our supply chain risk in the event that WuXi Biologics, Samsung Biologics or one of our other manufacturers or other supply chain vendors is impacted, including by continuing to identify and select additional source suppliers, including those based in the U.S.

and EU, for our contract development, manufacturing, testing, and storage needs.

We will also continue to closely monitor geopolitical risk and implement additional mitigations and supply chain redundancies, as needed.

We will also continue to closely monitor geopolitical risk and implement additional mitigation plans and supply chain redundancies, as needed.

See the section titled, Risk Factor - Risks Related to Our Reliance on Third Parties - “ We currently rely, and plan to rely in the future, on third parties to conduct and support our preclinical studies and clinical trials.

1 unchanged sentence

Intellectual Property

We strive to protect the proprietary programs and technologies that we believe are important to our business, including seeking and maintaining patent protection intended to cover the composition of matter of our programs, their methods of use, related technologies, diagnostics, and other inventions.

We strive to protect the proprietary product candidates and technologies that we believe are important to our business, including seeking and maintaining patent protection intended to cover the composition of matter of our product candidates, their methods of use, related technologies, diagnostics, and other inventions.

Patent Rights Relating to Our IL-13 Program

As of January 31, 2025, we own eight patent families directed to antibodies that target IL-13, including APG777, pharmaceutical formulations and compositions, and methods of using those antibodies.

As of January 31, 2026, we own eight patent families directed to antibodies that target IL-13, including zumilokibart (APG777), pharmaceutical formulations and compositions, and methods of using those antibodies.

The first patent family is directed to compositions of matter and includes patent applications filed in the U.S.

and in foreign jurisdictions including Europe, Japan and China.

If issued, we would expect these patents to expire in 2043, absent any applicable patent term extensions.

The second patent family is directed to methods of using APG777 and includes an international (PCT) patent application and applications in Argentina and Taiwan.

If the PCT application is pursued in the U.S.

or any foreign jurisdictions and matures into one or more issued patents, or the Argentina or Taiwan applications mature into issued patents, we would expect those patents to expire in 2044, absent any applicable patent term extensions.

The third patent family is directed to pharmaceutical formulations containing APG777 and includes a PCT application.

patent in this family issued on July 15, 2025;

We expect this patent to expire on June 16, 2043, absent any applicable patent term extension.

If other patents issue from this family we would expect these patents to expire in 2043, absent any applicable patent term extensions.

The second patent family is directed to methods of using zumilokibart and includes patent applications filed in the U.S.

and in foreign jurisdictions, including Europe, Japan and China.

If any of these patent applications mature into one or more issued patents, we would expect those patents to expire in 2044, absent any applicable patent term extensions.

The third patent family is directed to pharmaceutical formulations containing zumilokibart and includes a Patent Cooperation Treaty (“PCT”) application.

If the PCT application is pursued in the U.S.

or any foreign jurisdictions and matures into one or more issued patents, we would expect those patents to expire in 2044, absent any applicable patent term extensions.

The fourth patent family is directed to other APG777 compositions and includes a PCT application and applications filed in Argentina and Taiwan.

The fourth patent family is directed to other zumilokibart compositions and includes a PCT application and applications filed in Argentina and Taiwan.

If the PCT application is pursued in the U.S.

or any foreign jurisdictions and matures into one or more issued patents, or the Argentina or Taiwan applications mature into one or more issued patents, we would expect those patents to expire in 2044, absent any applicable patent term extensions.

The remaining four patent families are directed to other APG777 compositions and methods of using APG777 and each family, as of January 31, 2025, includes between one and three provisional applications.

If these provisional applications are pursued non-provisionally and mature into one or more issued patents, we would expect those patents to expire in 2045 and 2046, absent any applicable patent term extensions.

Patent Rights Relating to Our IL‑4Ra Program

As of January 31, 2025, we own four patent families directed to antibodies that target IL-4Ra, including APG808, and methods of using those antibodies.

The first patent family includes a PCT application and patent applications in Argentina and Taiwan.

The fifth patent family is directed to methods of administering zumilokibart and includes a PCT

If the PCT application is pursued in the U.S.

or any foreign jurisdictions and matures into one or more issued patents, or the Argentina or Taiwan applications mature issued patents, we would expect those patents to expire in 2044, absent any applicable patent term extensions.

The second patent family is directed to methods of using APG808 and includes a PCT application.

or any foreign jurisdictions and matures into one or more issued patents, we would expect those patents to expire in 2045, absent any applicable patent term extensions.

The sixth patent family is directed to compositions of zumilokibart in combination with hyaluronidase or a variant thereof and includes a PCT application.

If the PCT application is pursued in the U.S.

or any foreign jurisdictions and matures into one or more issued patents, we would expect those patents to expire in 2045, absent any applicable patent term extensions.

The remaining two patent families are directed to APG808 compositions and methods of using APG808 and as of January 31, 2025, each family includes one provisional patent application.

If these provisional applications are pursued non-provisionally and mature into one or more issued patents, we would expect those patents to expire in 2045, absent any applicable patent term extensions.

The seventh patent family is directed to the administration of zumilokibart to treat asthma and includes a PCT application.

If the PCT application is pursued in the U.S.

or any foreign jurisdictions and matures into one or more issued patents, we would expect those patents to expire in 2046, absent any applicable patent term extensions.

The remaining patent family is directed to compositions of anti-IL-13 antibodies and, as of January 31, 2026, includes one provisional application.

If this provisional application is pursued non-provisionally and matures into one or more issued patents, we would expect those patents to expire in 2046, absent any applicable patent term extensions.

Patent Rights Relating to Our OX40L Program

As of January 31, 2026, we own four patent families directed to antibodies that target OX40L, including APG990, and methods of using those antibodies and formulations thereof.

The first patent family includes a PCT application and applications in Argentina and Taiwan.

The first patent family has applications pending in the U.S.

and in foreign jurisdictions including Europe, Japan and China.

If any of these applications matures into one or more issued patents, we would expect those patents to expire in 2044, absent any applicable patent term extensions.

The second patent family is directed to methods of administering anti-OX40L antibodies and includes a PCT application.

If the PCT application is pursued in the U.S.

or any foreign jurisdictions and matures into an issued patent or the Argentina or Taiwan applications are pursued and mature into issued patents, we would expect those patents to expire in 2044, absent any applicable patent term extensions.

The second, third and fourth patent families are directed to pharmaceutical formulations and compositions including APG990 and methods of using APG990 and as of January 31, 2025, each family includes one or two provisional applications.

or any foreign jurisdiction and matures into one or more issued patents, we would expect those patents to expire in 2045, absent any applicable patent term extensions.

The third patent family is directed to compositions of APG990 in combination with hyaluronidase or a variant thereof and includes a U.S.

application matures into an issued patent, we would expect that patent to expire in 2045, absent any applicable patent term extensions.

The fourth patent family is directed to pharmaceutical formulations including APG990 and includes a PCT application.

If the PCT application is pursued in the U.S.

or any foreign jurisdiction and matures into one or more issued patents, we would expect those patents to expire in 2045, absent any applicable patent term extensions.

Patent Rights Relating to Our TSLP Program

As of January 31, 2025, we have licensed one patent family from Paragon directed to antibodies that target TSLP, including APG333, and methods of using those antibodies.

As of January 31, 2025, this family includes three provisional applications.

We also own two patent families directed to compositions of TSLP antibodies, including APG333, and methods of using APG333.

As of January 31, 2025, each of these families includes one provisional application.

As of January 31, 2026, we have licensed one patent family from Paragon directed to antibodies that target TSLP that have half-life extending mutations made to the Fc region of the antibody.

This family includes applications in the U.S., Europe, Japa and China.

If these applications are pursued and mature into one or more issued patents, we would expect those patents to expire in 2044, absent any applicable patent term extensions.

We have also licensed one patent family from Paragon directed to antibodies that target TSLP, including APG333, and methods of using those antibodies.

This family includes a PCT application and applications filed in Argentina and Taiwan.

If this PCT application is pursued in the U.S.

or any foreign jurisdiction and matures into one or more issued patents, or the Argentinian or Taiwanese applications are pursued and mature into one or more issued patents, we would expect those patents to expire in 2045, absent any applicable patent term extensions.

We also own two patent families directed to anti-TSLP antibodies, including APG333.

One family is directed to methods of administering anti-TSLP antibodies, including APG333, and includes a PCT application.

If the PCT application is pursued in the U.S.

or any foreign jurisdiction and matures into one or more issued patents, we would expect those patents to expire in 2045, absent any applicable patent term extensions.

The other family is directed to compositions of anti-TSLP antibodies such as APG333 in combination with hyaluronidase or a variant thereof and includes a U.S.

application matures into an issued patent, we would expect that patent to expire in 2045, absent any applicable patent term extensions.

Patent Rights Relating to Our IL‑4Ra Program

As of January 31, 2026, we own four patent families directed to antibodies that target IL-4Ra, including APG808, and methods of using those antibodies.

The first patent family includes applications filed in the U.S.

and in foreign jurisdictions including Europe, Japan and China.

If any of these applications matures into one or more issued patents, we would expect those patents to expire in 2044, absent any applicable patent term extensions.

The second patent family is directed to methods of using APG808 and includes a PCT application.

If the PCT application is pursued in the U.S.

or any foreign jurisdictions and matures into one or more issued patents, we would expect those patents to expire in 2045, absent any applicable patent term extensions.

The third patent family is directed to

compositions of APG808 in combination with hyaluronidase or a variant thereof and includes a PCT application.

If the PCT application is pursued in the U.S.

or any foreign jurisdictions and matures into one or more issued patents, we would expect those patents to expire in 2045, absent any applicable patent term extensions.

The fourth patent family is directed to combinations of anti-IL-4Ra and anti-TSLP or anti-TSLPR antibodies and, as of January 31, 2026, includes two provisional applications.

If these provisional applications are pursued non-provisionally and mature into one or more issued patents, we would expect those patents to expire in 2046, absent any applicable patent term extensions.

Patent Rights Relating to Our Combination Programs

As of January 31, 2025, we own six patent families directed to combinations of APG777, APG990, APG333 and/or APG808 and pharmaceutical formulations and compositions thereof.

As of January 31, 2025, each of these families includes between one and three provisional applications.

As of January 31, 2026, we own seven patent families directed to combinations of zumilokibart, APG990 (as a combination partner with zumilokibart for APG279), APG333 (as a combination partner with zumilokibart for APG273), and/or APG808, methods of administration and/or pharmaceutical formulations and compositions thereof.

The first family is directed to combinations of anti-IL-13 antibodies and anti-OX40L antibodies and includes a PCT application, as well as applications in Argentina and Taiwan.

If the PCT application is pursued in the U.S.

or any foreign jurisdiction and matures into one or more issued patents, or if the Argentinian or Taiwanese applications mature into one or more issued patents, we would expect those patents to expire in 2045, absent any applicable patent term extensions.

The second family is directed to combinations of anti-IL-4Ra antibodies and anti-OX40L antibodies and includes a PCT application.

If the PCT application is pursued in the U.S.

or any foreign jurisdiction and matures into one or more issued patents, we would expect those patents to expire in 2045, absent any applicable patent term extensions.

The third family is directed to co-formulations of anti-IL-13 antibodies such as zumilokibart and anti-OX40L antibodies such as APG990 and includes a PCT application.

If the PCT application is pursued in the U.S.

or any foreign jurisdiction and matures into one or more issued patents, we would expect those patents to expire in 2045, absent any applicable patent term extensions.

The fourth family is directed to combinations of anti-IL-13 antibodies such as zumilokibart and anti-TSLP antibodies such as APG333 in further combination with hyaluronidase or a variant thereof and includes a PCT application.

If the PCT application is pursued in the U.S.

or a foreign jurisdiction and matures into one or more issued patents, we would expect those patents to expire in 2045, absent applicable patent term extensions.

The fifth family is directed to combinations of anti-IL-4Ra antibodies such as APG808 and anti-TSLP antibodies such as APG333 in further combination with hyaluronidase or a variant thereof and includes a PCT application.

If the PCT application is pursued in the U.S.

or a foreign jurisdiction and matures into one or more issued patents, we would expect those patents to expire in 2045, absent any applicable patent term extensions.

The sixth family is directed to combinations of anti-OX40L antibodies such as APG990 and anti-TSLP antibodies such as APG333 in further combination with hyaluronidase or a variant thereof and includes a U.S.

application is pursued and matures into one or more issued patents, we would expect those patents to expire in 2045, absent any applicable patent term extensions.

The seventh family is directed to methods of administering anti-IL-13 antibodies such as zumilokibart in combination with anti-OX40L antibodies such as APG990 and, as of January 31, 2026, includes three provisional applications.

We have also licensed three patent families from Paragon directed to combinations of APG777, APG990, APG333 and/or APG808 and methods of using those combinations.

As of January 31, 2025, each of these families includes between one and three provisional applications.

We have also licensed three patent families from Paragon directed to combinations of APG333 with zumilokibart, APG808 and APG990 and methods of using those combinations.

Each of the three families includes a PCT application, as well as applications in Argentina and Taiwan.

If the PCT application is pursued in the U.S.

or a foreign jurisdiction and matures into one or more issued patents, or if the Argentinian or Taiwanese patent applications mature into one or more issued patents, we would expect those patents to expire in 2045, absent any applicable patent term extensions.

In addition, we have four other patent families that are directed to half-life-extended antibodies to different targets.

As of January 31, 2026, each of these four patent families has between one and two provisional applications filed.

2 unchanged sentences

If we do not timely file any non-provisional patent applications, we may lose our priority date with respect to our provisional patent applications and any patent protection on the inventions disclosed in our provisional patent applications.

While we intend to timely file non-provisional patent applications relating to our provisional patent applications, we cannot predict whether any such patent applications will result in the issuance of patents that provide us with any competitive advantage.

While we intend to timely file non-provisional patent applications relating to our provisional patent

applications, we cannot predict whether any such patent applications will result in the issuance of patents that provide us with any competitive advantage.

Moreover, the patent application and approval processes are expensive and time-consuming.

72 unchanged sentences

The IND also includes results of animal and in vitro studies assessing the toxicology, pharmacokinetics, pharmacology and pharmacodynamic characteristics of the product, chemistry, manufacturing and controls information, and any available human data or literature to support the use of the investigational product.

In April 2025, the FDA published a roadmap to reduce animal testing in preclinical safety studies, including those required in INDs, with scientifically validated new approach methodologies (“NAMs”).

An IND must become effective before human clinical trials may begin.

4 unchanged sentences

Clinical trials are conducted under protocols detailing, among other things, the objectives of the study, the parameters to be used in monitoring safety and the effectiveness criteria to be evaluated.

A separate submission to the existing IND must be made for each successive clinical trial conducted during product development and for any subsequent protocol amendments.

A separate submission to the existing IND must be made for each successive

clinical trial conducted during product development and for any subsequent protocol amendments.

Furthermore, an independent IRB for each site proposing to conduct the clinical trial must review and approve the plan for any clinical trial and its informed consent form before the clinical trial begins at that site, and must monitor the study until completed.

20 unchanged sentences

Assuming successful completion of all required testing in accordance with all applicable regulatory requirements, the results of product development, nonclinical studies and clinical trials are submitted to the FDA as part of a BLA requesting approval to market the product for one or more indications.

The BLA must include all relevant data available from pertinent preclinical studies and clinical trials, including negative or ambiguous results as well as positive findings, together with detailed information relating to the product’s chemistry, manufacturing, controls, and proposed labeling, among other things.

The BLA must include all relevant data available from pertinent preclinical studies and clinical trials, including negative or ambiguous results

as well as positive findings, together with detailed information relating to the product’s chemistry, manufacturing, controls, and proposed labeling, among other things.

Data can come from company-sponsored clinical studies intended to test the safety and effectiveness of the product, or from a number of alternative sources, including studies initiated and sponsored by investigators.

2 unchanged sentences

The Food and Drug Administration Safety and Innovation Act requires that a sponsor who is planning to submit a marketing application for a biological product that includes a new active ingredient, new indication, new dosage form, new dosing regimen or new route of administration submit an initial pediatric study plan (“PSP”) within 60 days after an end-of-Phase 2 meeting or as may be agreed between the sponsor and FDA.

Unless otherwise required by regulation, PREA does not apply to any biological product for an indication for which orphan designation has been granted.

Unless otherwise required by regulation, PREA does not apply to any biological product for an indication for which orphan designation has been granted, except that the PREA will apply to an original BLA for a new active ingredient that is orphan-designated if the biologic is a molecularly targeted cancer product intended for the treatment of an adult cancer and is directed at a molecular target that the FDA determines to be substantially relevant to the growth or progression of a pediatric cancer.

Within 60 days following submission of the application, the FDA reviews a BLA submitted to determine if it is substantially complete before the agency accepts it for filing.

8 unchanged sentences

The FDA will not approve an application unless it determines that the manufacturing processes and facilities are in compliance with cGMP requirements and adequate to assure consistent production of the product within required specifications.

Additionally, before approving a BLA, the FDA will typically

inspect one or more clinical sites to assure compliance with GCPs.

Additionally, before approving a BLA, the FDA will typically inspect one or more clinical sites to assure compliance with GCPs.

If the FDA determines that the application, manufacturing process or manufacturing facilities are not acceptable, it will outline the deficiencies in the submission and often will request additional testing or information.

7 unchanged sentences

For example, the FDA may approve the BLA with a risk evaluation and mitigation strategy (“REMS”) to ensure the benefits of the product outweigh its risks.

A REMS is a safety strategy to manage a known or potential serious risk associated with a product and to enable patients to have continued access to such medicines by managing their safe use, and could include medication guides, physician communication plans, or elements to assure safe use, such as restricted distribution methods, patient registries and other risk minimization tools.

physician communication plans, or elements to assure safe use, such as restricted distribution methods, patient registries and other risk minimization tools.

The FDA also may condition approval on, among other things, changes to proposed labeling or the development of adequate controls and specifications.

34 unchanged sentences

Given the wide range of potential combination therapy variations, the FDA indicated it intends to assess each potential combination on a case-by case basis and encouraged sponsors to engage in early and regular consultation with the relevant review division at the agency throughout the development process for its proposed combination.

Regulation of Combination Products

Certain therapeutic products are comprised of multiple components, such as drug components, biologic components, and device components, that would normally be subject to different regulatory frameworks by the FDA and frequently regulated by different centers at the FDA.

These products are known as combination products.

Under the FDCA, the FDA is charged with assigning a center with primary jurisdiction, or a lead center, for review of a combination product.

The determination of which center will be the lead center is based on the “primary mode of action” of the combination product.

Thus, if the primary mode of action of a drug/biologic-device combination product is attributable to the drug or biological product, the FDA center responsible for premarket review of the drug or biological product would have primary jurisdiction for the combination product.

The FDA has also established the Office of Combination Products to address issues surrounding combination products and provide more certainty to the regulatory review process.

That office serves as a focal point for combination product issues for agency reviewers and industry.

It is also responsible for developing guidance and regulations to clarify the regulation of combination products, and for assignment of the FDA center that has primary jurisdiction for review of combination products where the jurisdiction is unclear or in dispute.

A combination product with a primary mode of action attributable to the biologic component generally would be reviewed and approved pursuant to the biologic approval processes set forth in the FDCA.

In reviewing the BLA for such a product, however, FDA reviewers would consult with their counterparts in the FDA’s Center for Devices and Radiological Health to ensure that the device component of the combination product met applicable requirements regarding safety, effectiveness, durability and performance.

In addition, under FDA regulations, combination products with both device and drug/biologic components are subject to cGMP requirements applicable to both drugs and devices, including the Quality Management System Regulation applicable to medical devices.

Post-Approval Requirements

Any products manufactured or distributed by us pursuant to FDA approvals are subject to pervasive and continuing regulation by the FDA, including, among other things, requirements relating to record-keeping, reporting of adverse experiences, periodic reporting, product sampling and distribution, and advertising and promotion of the product.

As part of the manufacturing process, the manufacturer is required to perform certain tests on each lot of the product before it is released for distribution.

As part of the manufacturing process, the manufacturer is required to perform certain tests on each lot of the

product before it is released for distribution.

After a BLA is approved for a biological product, the product also may be subject to official lot release.

1 unchanged sentence

The FDA also may perform certain confirmatory tests on lots of some products before releasing the lots for distribution by the manufacturer.

In addition, the FDA conducts laboratory research related to the regulatory standards on the safety,

purity, and potency or effectiveness of biologics.

In addition, the FDA conducts laboratory research related to the regulatory standards on the safety, purity, and potency or effectiveness of biologics.

After approval, most changes to the approved product, such as adding new indications or other labeling claims, are subject to prior FDA review and approval.

27 unchanged sentences

Biosimilars and Reference Product Exclusivity

The ACA includes a subtitle called the BPCIA, which created an abbreviated approval pathway for biological products that are highly similar, or “biosimilar,” to or interchangeable with an FDA-approved reference biological product.

The Patient Protection and Affordable Care Act, as amended by the Healthcare and Education Reconciliation Act (“ACA”) includes a subtitle called the Biologics Price Competition and Innovation Act of 2009 (“BPCIA”), which created an abbreviated approval pathway for biological products that are highly similar, or “biosimilar,” to or interchangeable with an FDA-approved reference biological product.

The FDA has issued several guidance documents outlining an approach to review and approval of biosimilars.

15 unchanged sentences

The BPCIA is complex and continues to be interpreted and implemented by the FDA.

In July 2018, the FDA announced an action plan to encourage the development and efficient review of biosimilars, including the establishment of a new office within the agency that will focus on therapeutic biologics and biosimilars.

On December 20, 2020, Congress amended the PHSA as part of the COVID‑19 relief bill to further simplify the biosimilar review process by making it optional to show that conditions of use proposed in labeling have been previously approved for the reference product, which used to be a requirement of the application.

2 unchanged sentences

As a result, the ultimate impact, implementation, and impact of the BPCIA is subject to significant uncertainty.

As discussed below, the Inflation Reduction Act of 2022 (IRA) is a significant new law that intends to foster generic and biosimilar competition and to lower drug and biologic costs.

As discussed below, the Inflation Reduction Act of 2022 (the “IRA”) is a law that intends to foster generic and biosimilar competition and to lower drug and biologic costs.

Other Healthcare Laws and Compliance Requirements

8 unchanged sentences

The government often takes the position that to violate the AKS, only one purpose of the remuneration need be to induce referrals, even if there are other legitimate purposes for the remuneration.

There are a number of statutory exceptions and regulatory safe harbors protecting some common activities from AKS prosecution, but they are drawn narrowly and practices that involve remuneration, such as consulting agreements, that may be alleged to be intended to induce prescribing, purchasing or recommending may be subject to scrutiny if they do not qualify for an exception or safe harbor.

There are a number of statutory exceptions and regulatory safe harbors protecting some common commercial activities from AKS prosecution, but they are drawn narrowly and practices that involve remuneration, such as consulting agreements, for persons in a position to refer or recommend federally reimbursable healthcare business may be alleged to be intended to induce prescribing, purchasing or recommending, and may be subject to scrutiny if they do not qualify for an exception or regulatory safe harbor.

Qualifying for a statutory exception or regulatory safe harbor requires satisfying all of the criteria for the exception or safe harbor.

Our practices may not in all cases meet all of the criteria for protection under a statutory exception or regulatory safe harbor.

Failure to meet all of the requirements of a particular applicable statutory exception or regulatory safe harbor does not make the conduct per se illegal under the AKS.

Instead, the legality of the arrangement will be evaluated on a case-by-case basis based on a cumulative review of all of its facts and circumstances.

Failure to meet all of the requirements of a particular applicable statutory exception or regulatory safe harbor does not make the conduct per se illegal under the AKS, but it does increase the risk of regulatory scrutiny.

Ultimately, the legality of the arrangement will be evaluated on a case-by-case basis based on a cumulative review of all of its facts and circumstances.

A person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation.

Civil and criminal false claims laws, including the FCA, and civil monetary penalty laws, which can be enforced through civil whistleblower or qui tam actions, prohibit, among other things, individuals or entities from knowingly presenting, or causing to be presented, claims for payment of federal government funds, including in federal healthcare programs, that are false or fraudulent.

The FCA, which can be enforced through civil whistleblower or qui tam actions, prohibits, among other things, individuals or entities from knowingly presenting, or causing to be presented, claims for payment of federal government funds, including in federal healthcare programs, that are false or fraudulent.

Pharmaceutical and other healthcare companies have been prosecuted under these laws for engaging in a variety of different types of conduct that caused the submission of false claims to federal healthcare programs.

14 unchanged sentences

Numerous state, federal, and foreign laws govern the collection, dissemination, use, access to, confidentiality, and security of personal information, including health-related information.

In the United States, numerous federal and state laws and regulations, including state data breach notification laws, state health information privacy laws, and federal and state consumer protection laws and regulations, govern the collection, use, disclosure, and protection of health-related and other personal information could apply to our operations or the operations of our partners.

For example, HIPAA, as amended by the Health Information Technology for Economic and Clinical Health (“HITECH”), and their respective implementing regulations imposes data privacy, security, and breach notification obligations on certain health care providers, health plans, and health care clearinghouses, known as covered entities, as well as their business associates and their covered subcontractors that perform certain services that involve using, disclosing, creating, receiving, maintaining, or transmitting individually identifiable protected health information (“PHI”) for or on behalf of such covered entities.

These requirements imposed by HIPAA and the HITECH Act on covered entities and business associates include entering into agreements that require business associates protect PHI provided by the covered entity against improper use or disclosure, among other things;

In the United States, numerous federal and state laws and regulations, including state data breach notification laws, state health information privacy laws, and federal and state consumer protection laws and regulations, govern the collection, use, disclosure, and protection of health-related and other personal information and could apply to our operations or the operations of our partners.

For example, HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act (“HITECH”), and their respective implementing regulations impose data privacy, security, and breach notification obligations on certain health care providers, health plans, and health care clearinghouses, known as covered entities, as well as their business associates and their covered subcontractors that perform certain services that involve using, disclosing, creating, receiving, maintaining, or transmitting individually identifiable protected health information (“PHI”) for or on behalf of such covered entities.

These requirements imposed by HIPAA and HITECH on covered entities and business associates include entering into agreements that require business associates to protect PHI provided by the covered entity against improper use or disclosure, among other things;

following certain standards for the privacy of PHI, which limit the disclosure of a patient’s past, present, or future physical or mental health or condition or information about a patient’s receipt of health care if the information identifies, or could reasonably be used to identify, the individual;

5 unchanged sentences

To the extent that we submit electronic healthcare claims and payment transactions that do not comply with the electronic data transmission standards established under HIPAA and HITECH, payments to us may be delayed or denied.

In addition, state health information privacy laws, such as California’s Confidentiality of Medical Information Act and Washington’s My Health My Data Act, govern the privacy and security of health-related information, specifically, may apply even when HIPAA does not and impose additional requirements.

Even when HIPAA and state health information privacy laws do not apply, according to the FTC and state Attorneys General, violating consumers’ privacy rights or failing to take appropriate steps to keep consumers’ personal information secure may constitute unfair acts or practices in or affecting commerce in violation of Section 5(a) of the Federal Trade Commission Act and state consumer protection laws.

In addition, state health information privacy laws, such as California’s Confidentiality of Medical Information Act, Washington’s My Health My Data Act, and the Connecticut Data Privacy Act (as amended by Public-Act 23-145) that govern the privacy and security of health-related information, specifically, may apply even when HIPAA does not and impose additional requirements.

Even when HIPAA and state health information privacy laws do not apply, according to the FTC and state attorneys general, violating consumers’ privacy rights or failing to take appropriate steps to keep consumers’ personal

information secure may constitute unfair acts or practices in or affecting commerce in violation of Section 5(a) of the Federal Trade Commission Act and state consumer protection laws.

In addition, certain state laws, such as the California Consumer Privacy Act of 2018 (“CCPA”), as amended by the California Privacy Rights Act of 2020, govern the privacy and security of personal information, including health-related information in certain circumstances, some of which are more stringent than HIPAA in various ways.

Numerous other states have passed similar laws, but many differ from each other in significant ways and may not

have the same effect, thus complicating compliance efforts.

Numerous other states have passed similar laws, but many differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts.

The CCPA applies to personal data of consumers, business representatives, and employees, and imposes obligations on certain businesses that do business in California, including to provide specific disclosures in privacy notices, and affords rights to California residents in relation to their personal information.

Health information falls under the CCPA’s definition of personal information where it identifies, relates to, describes, or is reasonably capable of being associated with or could reasonably be linked, directly or indirectly, with a particular consumer or household — unless it is subject to HIPAA — and is included under a new category of personal information, “sensitive personal information,” which is offered greater protection.

The numerous other comprehensive privacy laws that have passed or are being considered in other states, as well as at the federal and local levels, also exempt some data processed in the context of clinical trials;

but others exempt covered entities and business associates subject to HIPAA altogether, further complicating compliance efforts, and increasing legal risk and compliance costs for us and the third parties upon whom we rely.

Additionally, our use of artificial intelligence and machine learning may be subject to laws and evolving regulations regarding the use of artificial intelligence and machine learning, controlling for data bias, and antidiscrimination.

Health information falls under the CCPA’s definition of personal information where it identifies, relates to, describes, or is reasonably capable of being associated with or could reasonably be linked, directly or indirectly, with a particular consumer or household and is included under a new category of personal information, “sensitive personal information”, which is offered greater protection.

The CCPA and numerous other comprehensive privacy laws that have passed or are being considered in other states, as well as at the federal and local levels, exempt PHI that is subject to HIPAA;

and others exempt covered entities and business associates subject to HIPAA altogether, further complicating compliance efforts, and increasing legal risk and compliance costs for us and the third parties upon whom we rely.

Additionally, our use of artificial intelligence (”AI”) and machine learning may be subject to laws and evolving regulations regarding the use of AI and machine learning, controlling for data bias, and antidiscrimination.

Failure to comply with these laws, where applicable, can result in the imposition of significant civil and/or criminal penalties and private litigation.

3 unchanged sentences

Adequate coverage and reimbursement from governmental healthcare programs, such as Medicare and Medicaid, and commercial payors is critical to new product acceptance.

Our ability to successfully commercialize our product candidates will depend in part on the extent to which coverage and adequate reimbursement for these products and related treatments will be available from government health administration authorities, private health insurers and other organizations.

Our ability to successfully commercialize our product candidates will depend in part on the extent to which coverage and adequate reimbursement for these product candidates and related treatments will be available from government health administration authorities, private health insurers and other organizations.

Even if coverage is provided, the approved reimbursement amount may not be high enough to allow it to establish or maintain pricing sufficient to realize a sufficient return on its investment.

11 unchanged sentences

• neither experimental nor investigational.

Third-party payors are increasingly challenging the prices charged for medical products and services, examining the medical necessity and reviewing the cost effectiveness of pharmaceutical or biological products, medical devices

and medical services, in addition to questioning safety and efficacy.

Adoption of price controls and cost-containment measures, and adoption of more restrictive policies in jurisdictions with existing controls and measures, could further limit sales of any product that receives approval.

18 unchanged sentences

In addition, net prices for drugs may be reduced by mandatory discounts or rebates required by government healthcare programs or private payors and by any future relaxation of laws that presently restrict imports of drugs from countries where they may be sold at lower prices than in the U.S.

Increasingly, third-party payors are requiring that drug companies provide them with predetermined rebates from list prices.

Increasingly, third-party payors are requiring that drug companies provide them with predetermined discounts from list prices and are challenging the prices charged for medical products.

We cannot be sure that reimbursement will be available for any product candidate that we may commercialize and, if reimbursement is available, the level of reimbursement.

7 unchanged sentences

A member state may approve a specific price for the medicinal product or it may instead adopt a system of direct or indirect controls on the profitability of the company placing the medicinal product on the market.

There can be no assurance that any country that has price controls or reimbursement limitations for pharmaceutical products will allow favorable reimbursement and pricing arrangements for any of our product candidates.

There can be no assurance that any country that has price controls or reimbursement limitations for pharmaceutical products will allow favorable reimbursement

and pricing arrangements for any of our product candidates.

Historically, products launched in the European Union do not follow price structures of the U.S.

3 unchanged sentences

There is significant interest in promoting changes in healthcare systems with the stated goals of containing healthcare costs, improving quality or expanding access.

In the United States, the pharmaceutical industry has been a particular focus of these efforts and has been significantly affected by federal and

state legislative initiatives, including those designed to limit the pricing, coverage, and reimbursement of pharmaceutical and biopharmaceutical products, especially under government-funded health care programs, and increased governmental control of drug pricing.

In the United States, the pharmaceutical industry has been a particular focus of these efforts and has been significantly affected by federal and state initiatives, including those designed to limit the pricing, coverage, and reimbursement of pharmaceutical and biopharmaceutical products, especially under government-funded health care programs, and increased governmental control of drug pricing.

The ACA, which was enacted in March 2010, substantially changed the way healthcare is financed by both governmental and private insurers in the United States, and significantly affected the pharmaceutical industry.

8 unchanged sentences

For example, in May 2019, CMS adopted a final rule allowing Medicare Advantage Plans the option to use step therapy for Part B drugs, permitting Medicare Part D plans to apply certain utilization controls to new starts of five of the six protected class drugs, and requiring the Explanation of Benefits for Part D beneficiaries to disclose drug price increases and lower cost therapeutic alternatives, which went into effect on January 1, 2021.

In response to the Biden administration’s October 2022 executive order, on February 14, 2023, HHS released a report outlining three new models for testing by the CMS Innovation Center which will be evaluated on their ability to lower the cost of drugs, promote accessibility, and improve quality of care.

It is unclear whether the models will be utilized in any health reform measures in the future.

Further, on December 7, 2023, the Biden administration announced an initiative to control the price of prescription drugs through the use of march-in rights under the Bayh-Dole Act.

On December 8, 2023, the National Institute of Standards and Technology published for comment a Draft Interagency Guidance Framework for Considering the Exercise of March-In Rights which for the first time includes the price of a product as one factor an agency can use when deciding to exercise march-in rights.

While march-in rights have not previously been exercised, it is uncertain if that will continue under the new framework.

In May 2025, the Trump Administration renewed the idea of international reference pricing through an executive order entitled “Delivering Most-Favored-Nation Prescription Drug Pricing to American Patients,” which, among other things, directs the HHS and other agencies to communicate most-favored-nation price targets to pharmaceutical manufacturers to bring prices for U.S.

patients in line with comparably developed nations and to facilitate direct-to-consumer purchasing programs.

The HHS subsequently issued guidance indicating the MFN target price will be the lowest price paid in an Organisation for Economic Co-operation and Development country with a gross domestic product (“GDP”) per capita of at least 60% of the U.S.

GDP per capital.

In addition, in December 2025, CMS proposed new drug payment models to lower drug prices for Medicare beneficiaries;

under the models, CMS would explore potential adjustments to Medicare drug inflation rebate calculations by comparison to international drug pricing information.

It is currently unclear whether and to what extent these measures will be implemented and what impact any such implementation would have on our business.

Notwithstanding the IRA, continued legislative and enforcement interest exists in the United States with respect to specialty drug pricing practices.

Specifically, we expect regulators to continue pushing for transparency to drug pricing, reducing the cost of prescription drugs under Medicare, reviewing the relationship between pricing and manufacturer patient programs, and reforming government program reimbursement methodologies for drugs.

Specifically, we expect government authorities to continue pushing for transparency to drug pricing, reducing the cost of prescription drugs under Medicare, reviewing the relationship between pricing and manufacturer patient programs, and reforming government program reimbursement methodologies for drugs.

Individual states in the U.S.

1 unchanged sentence

Legally mandated price controls on payment amounts by third-party payors or other restrictions could harm our business, financial condition, results of operations and prospects.

In addition, regional healthcare authorities and individual

hospitals are increasingly using bidding procedures to determine what pharmaceutical products and which suppliers will be included in their prescription drug and other healthcare programs.

This could reduce the ultimate demand for its drugs or put pressure on its drug pricing, which could negatively affect our business, financial condition, results of operations and prospects.

In addition, regional healthcare authorities and individual hospitals are increasingly using bidding procedures to determine what pharmaceutical products and which suppliers will be included in their prescription drug and other healthcare programs.

This could reduce the ultimate demand for our drugs or put pressure on our drug pricing, which could negatively affect our business, financial condition, results of operations and prospects.

Other Government Regulation Outside of the United States

11 unchanged sentences

European Data Laws

The collection and use of personal health data and other personal data in the EU is governed by the provisions of the European General Data Protection Regulation (EU) 2016/679 (“GDPR”), which came into force in May 2018, and related data protection laws in individual EU Member States.

The GDPR imposes a number of strict obligations and restrictions on the ability to process, including collecting, analyzing and transferring, personal data of individuals, in particular with respect to health data from clinical trials and adverse event reporting.

The GDPR includes requirements relating to the legal basis of the processing (such as consent of the individuals to whom the personal data relates), the information provided to the individuals prior to processing their personal data, the personal data breaches which may have to be notified to the national data protection authorities and data subjects, the measures to be taken when engaging processors, and the security and confidentiality of the personal data.

EU Member States may also impose additional requirements in relation to health, genetic and biometric data through their national legislation.

In addition, the GDPR imposes specific restrictions on the transfer of personal data to countries outside of the European Economic Area (“EEA”) that are not considered by the European Commission (“EC”) to provide an adequate level of data protection.

The processing of personal data, including health-related personal data in the European Economic Area(“EEA”) is mainly governed by the provisions of the European General Data Protection Regulation (EU) 2016/679 (“GDPR”), and related data protection laws in individual EEA countries.

In the United Kingdom, the processing of personal data is mainly governed by the GDPR as incorporated into UK law pursuant to the European Union (Withdrawal) Act 2018 (the “UK GDPR”).

The GDPR and UK GDPR imposes a number of strict obligations and requirements for the processing, including collecting, analyzing and transferring, of personal data of individuals in the EEA or in the UK, in particular with respect to health data from clinical trials and adverse event reporting.

The GDPR and UK GDPR include requirements relating to the legal basis of the processing (such as consent of the individuals to whom the personal data relates), the information provided to the individuals prior to processing their personal data, the personal data breaches which may have to be notified to the national data protection authorities and data subjects, the measures to be taken when engaging processors, and obligations relating to the security and confidentiality of the personal data.

EEA countries may also impose additional requirements in relation to the processing of health, genetic and biometric data through their national legislation.

In addition, the GDPR imposes specific restrictions on the transfer of personal data to countries outside of the EEA that are not considered by the European Commission (“EC”) to provide an adequate level of data protection.

Appropriate safeguards are required to enable such transfers.

Among the appropriate safeguards that can be used, the data exporter may use the standard contractual clauses (“SCCs”).

When relying on SCCs, data exporters are also required to conduct a transfer risk assessment to verify if anything in the law and/or practices of the third country may impinge on the effectiveness of the SCCs in the context of the transfer at stake and, if so, to identify and adopt supplementary measures that are necessary to bring the level of protection of the data transferred to the EU standard of essential equivalence.

When relying on the appropriate safeguards, data exporters, with the assistance of the data importers, are also required to conduct a transfer risk assessment to verify if anything in the law and/or practices of the third country may impinge on the effectiveness of the safeguards in the context of the transfer at stake and, if so, to identify and adopt supplementary measures that are necessary to bring the level of protection of the data transferred to the EU standard of essential equivalence.

Where no supplementary measure is suitable, the data exporter should avoid, suspend or terminate the transfer.

2 unchanged sentences

companies participating in the framework.

With regard to the transfer of data from the EU to the United Kingdom (“UK”), personal data may freely flow from the EEA to the UK since the UK is deemed to have an adequate data protection level.

However, the adequacy decisions

include a ‘sunset clause’ which entails that the decisions will automatically expire four years after their entry into force, unless renewed.

Failure to comply with the requirements of the GDPR and the related national data protection laws of the EU Member States may result in significant monetary fines for noncompliance of up to €20 million or 4% of the annual global revenues of the noncompliant company, whichever is greater, other administrative penalties and a number of criminal offenses for organizations and, in certain cases, their directors and officers, as well as civil liability claims from individuals whose personal data was processed.

Data protection authorities from the different EU Member States may still implement certain variations, enforce the GDPR and national data protection laws differently, and introduce additional national regulations and guidelines, which adds to the complexity of processing personal data in the EU.

With regard to the transfer of data from the EEA to the UK, based on the EC’s adequacy decision of June 28, 2021 and subsequent renewals, personal data may continue to flow freely from the EEA to the UK on the basis that the UK is deemed to provide an adequate level of data protection until December 27, 2031.

The adequacy decisions will automatically expire unless renewed.

With respect to transfers from the UK to other countries, these transfers are also subject to specific transfer rules under the UK regime.

These UK international transfer rules broadly mirror the EU GDPR rules.

On February 2, 2022, the UK Secretary of State laid before the UK Parliament the international data transfer agreement (“IDTA”) and the international data transfer addendum to the EC’s standard contractual clauses for international data transfers (“UK Addendum”) and a document setting out transitional provisions.

The IDTA and UK Addendum came into force on March 21, 2022 and are the primary UK-approved mechanisms for putting in place appropriate safeguards for UK restricted transfers, subject to transitional arrangements for legacy SCCs.

Regarding transfers from the UK to the EEA, the UK Information Commissioner’s Office (“ICO”) guidance indicates that organizations do not need new arrangements.

With regard to the transfer of personal data from the UK to the United States, the UK government has adopted an adequacy decision for the UK Extension to the EU-US Data Privacy Framework, the UK-US Data Bridge, which came into force on October 12, 2023.

The UK-US Data Bridge recognizes the United States as offering an adequate level of data protection where the recipient is a U.S.

organization certified to the EU-US Data Privacy Framework and participating in the UK Extension to the EU-US Data Privacy Framework.

Failure to comply with the requirements of the GDPR or UK GDPR and the related national data protection laws of the EEA countries may result in significant monetary fines for noncompliance of up to €20 million or £17.5 million (as applicable), 4% of the total worldwide annual turnover (for higher-tier infringements).

This is enforced by ICO and is entirely separate from fines under EU GDPR.

In addition, violations of national laws can trigger additional, administrative penalties, investigations, corrective orders, temporary or definitive bans, and, in some jurisdictions, and a number of criminal offenses for organizations and, in certain cases, their directors and officers, as well as civil liability claims from individuals whose personal data was processed.

Data protection authorities from the different EEA countries may still implement certain variations, enforce the GDPR and national data protection laws differently, and introduce additional national regulations and guidelines, which adds to the complexity of processing personal data in the EEA.

Furthermore, there are specific requirements relating to processing health data from clinical trials, including public disclosure obligations provided in the EU Clinical Trials Regulation No.

536/2014 (CTR), EMA disclosure initiatives and voluntary commitments by industry.

536/2014 (“CTR”), European Medicines Agency (“EMA”) disclosure initiatives and voluntary commitments by industry.

Failure to comply with these obligations could lead to government enforcement actions and significant penalties against us, harm to our reputation, and adversely impact our business and operating results.

Additionally, following the UK’s withdrawal from the EU and the EEA, companies also have to comply with the UK’s data protection laws (including the UK GDPR (as defined in section 3(10) (as supplemented by section 205(4)) of the Data Protection Act 2018 (“DPA 2018”)), the DPA 2018, and related data protection laws in the UK).

Separate from the fines that can be imposed by the GDPR, the UK regime has the ability to fine up to the greater of £17.5 million or 4% of global turnover.

Companies are subject to specific transfer rules under the UK regime which broadly mirror the GDPR rules.

On February 2, 2022, the UK Secretary of State laid before the UK Parliament the international data transfer agreement (“IDTA”) and the international data transfer addendum to the EC’s standard contractual clauses for international data transfers (“Addendum”) and a document setting out transitional provisions.

The IDTA and Addendum came into force on March 21, 2022 and replaced the old SCCs for the purposes of the UK regime.

Regarding transfer from the UK to the EEA, personal data may flow freely since the EEA is deemed to have an adequate data protection level for purposes of the UK regime.

With regard to the transfer of personal data from the UK to the United States, the UK government has adopted an adequacy decision for the United States, the UK-US Data Bridge, which came into force on October 12, 2023.

The UK-US Data Bridge recognizes the United States as offering an adequate level of data protection where the transfer is to a U.S.

company participating in the EU-US Data Privacy Framework and the UK Extension.

Drug and Biologic Development Process

3 unchanged sentences

The CTR replaced the Clinical Trials Directive 2001/20/EC (“Clinical Trials Directive”) and introduced a complete overhaul of the existing regulation of clinical trials for medicinal products in the EU.

Under the new CTR, a sponsor is able to submit a single application for approval of a clinical trial through a centralized EU clinical trials portal (“the Clinical Trials Information System” or “CTIS”).

Under the CTR, a sponsor is able to submit a single application for approval of a clinical trial through a centralized EU clinical trials portal (the “Clinical Trials Information System” or “CTIS”).

One national regulatory authority (the reporting EU member state proposed by the applicant) will take the lead in validating and evaluating the application consult and coordinate with the other concerned EU Member States.

2 unchanged sentences

However, a concerned EU member state may in limited circumstances declare an “opt-out” from an approval and prevent the clinical trial from being conducted in such member state.

The CTR also aims to streamline and simplify the rules on safety reporting, and introduces enhanced transparency requirements such as mandatory submission of a summary of the clinical trial results to the EU Database.

Since January 31, 2023, submission of initial clinical trial applications via CTIS is mandatory and CTIS serves as the single entry point for submission of clinical trial-related information and data.

By January 31, 2025, all ongoing trials approved under the former Clinical Trials Directive will need to comply with the CTR and have to be transitioned to CTIS.

On July 19, 2023, the EC published guidance concerning the steps to be taken in this transition.

This guidance provides, among other things, that (i) documentation which was previously assessed will not be reassessed, (ii) templates that were developed and endorsed by the EU Clinical Trials Expert Group to provide compliance with the CTR do not need to be updated and (iii) there is no need to retrospectively create a site suitability form, which are only necessary for new trial sites.

Under both the former regime and the new CTR, national laws, regulations, and the applicable GCP and Good Laboratory Practice standards must also be respected during the conduct of the trials, including the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (“ICH”) guidelines on Good Clinical Practice and the ethical principles that have their origin in the Declaration of Helsinki.

As of January 31, 2025, all ongoing trials approved under the former Clinical Trials Directive need to comply with the CTR and have to be transitioned to CTIS.

Under the CTR, national laws, regulations, and the applicable GCP and GLP standards must also be respected during the conduct of the trials, including the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (“ICH”) guidelines on Good Clinical Practice and the ethical principles that have their origin in the Declaration of Helsinki.

Under the current regime, all suspected unexpected serious adverse reactions to the investigated drug that occur during the clinical trial must be reported to the National Competent Authority and to the Ethics Committees of the EU member state where they occur.

During the development of a medicinal product, the EMA and national regulators within the EU provide the opportunity for dialogue and guidance on the development program.

6 unchanged sentences

To obtain an MA of a drug under EU regulatory systems, an applicant can submit an MAA through, amongst others, a centralized or decentralized procedure.

To be used or sold in the UK, a drug must have an effective MA obtained by a centralized application through EMA or a national application.

National applications are governed by the Human Medicines Regulations (SI 2012/1916).

Applications are made electronically through the Medicines and Healthcare products Regulatory Agency (“MHRA”) Submissions Portal.

The process from application to authorizations generally takes up to 210 days, excluding time taken to provide any additional information or data required by the MHRA.

On August 30, 2023, the MHRA published detailed guidance on its recently announced new International Reliance Procedure (“IRP”) for MAAs.

The IRP applies since January 1, 2024 and replaces existing EU reliance procedures to apply for authorizations from seven international regulators (e.g.

Health Canada, Swiss Medic, FDA, EMA, among others).

To be used or sold in the UK, a drug must have an effective MA granted by the Medicines and Healthcare Products Regulatory Agency (“MHRA”) under the Human Medicines Regulations 2012 (SI 2012/1916), as amended.

MA applications are submitted electronically via the MHRA Submissions Portal.

Under the MHRA’s national assessment procedure, the MHRA generally aims to reach a decision within 210 “clock-on” days, excluding any “clock-stops” while the applicant prepares responses to MHRA questions.

On August 30, 2023, the MHRA published detailed guidance on its recently announced new International Recognition Procedure (“IRP”) for MAAs.

The IRP has applied since January 1, 2024 and replaces existing EU reliance procedures to apply for authorizations from seven international regulators (e.g.

Health Canada, Swiss Medic,

FDA, EMA, among others).

The IRP allows medicinal products approved in other jurisdictions that meet certain criteria to undergo a fast-tracked MHRA review to obtain and/or update a MA in the UK.

1 unchanged sentence

Centralized Authorization Procedure

The centralized procedure provides for the grant of a single MA that is issued by the EC following the scientific assessment of the application by the European Medicines Agency (“EMA”) that is valid for all EU Member States as well as in the three additional EEA Member States (Norway, Iceland and Liechtenstein).

The centralized procedure is compulsory for specific medicinal products, including for medicines developed by means of certain biotechnological processes, products designated as orphan medicinal products, advanced therapy medicinal products (gene therapy, somatic cell therapy, or tissue engineered medicines) and medicinal products with a new active substance indicated for the treatment of certain diseases (HIV/AIDS, cancer, neurodegenerative disorders, diabetes, auto-immune and viral diseases).

For medicinal products containing a new active substance not yet authorized in the EEA before May 20, 2004 and indicated for the treatment of other diseases, medicinal products that constitute significant therapeutic, scientific or technical innovations or for which the grant of a MA through the centralized procedure would be in the

interest of public health at EU level, an applicant may voluntarily submit an application for a MA through the centralized procedure.

Under the centralized procedure, the Committee for Medicinal Products for Human Use (“CHMP”) established at the EMA, is responsible for conducting the initial assessment of a drug.

The centralized procedure provides for the grant of a single MA that is issued by the EC following the scientific assessment of the application by the EMA that is valid for all EU Member States as well as in the three additional EEA Member States (Norway, Iceland and Liechtenstein).

Under the centralized procedure, the CHMP is responsible for conducting the initial assessment of a drug.

The CHMP is also responsible for several post-authorization and maintenance activities, such as the assessment of modifications or extensions to an existing MA.

25 unchanged sentences

After these five years, the authorization may subsequently be renewed on the basis of a reevaluation of the risk-benefit balance.

Once renewed, the MA is valid for an unlimited period unless the EC or the national competent authority decides, on justified grounds relating to pharmacovigilance, to proceed

with only one additional five-year renewal.

Once renewed, the MA is valid for an unlimited period unless the EC or the national competent authority decides, on justified grounds relating to pharmacovigilance, to proceed with only one additional five-year renewal.

Applications for renewal must be made to the EMA at least nine months before the five-year period expires.

1 unchanged sentence

For the UK, the period of three years during which the drug has not been marketed in Great Britain will be restarted from the date of conversion to a Great Britain MA.

Conversion refers to the procedure by which, as of January 1, 2021, MAs granted on the basis of a centralized procedure in the EU are only valid in Northern Ireland but not in Great Britain, whereas, prior EU authorizations have all been automatically converted into UK MAs effective in Great Britain only.

Following Windsor Framework changes, which became effective January 1, 2025, European Commission Union authorizations are no longer valid in Northern Ireland and centrally authorized products are instead authorized by the MHRA under UK-wide marketing authorizations;

existing licenses for product licensed by the MHRA that covers Great Britain only become geographically valid UK-wide while retaining their license number/prefix.

On the other hand, for the EU, in the case the drug has been marketed in the UK, the placing on the UK market before the end of the period starting when the UK left the EU on January 31, 2020 and ending on December 31, 2020 (the Brexit Transition Period) will be taken into account.

25 unchanged sentences

Even if a compound is considered to be a NCE and the MA applicant is able to gain the prescribed period of data exclusivity, another company nevertheless could also market another version of the medicinal product if such company can complete a full MAA with their own complete database of pharmaceutical tests, preclinical studies and clinical trials and obtain MA of its product.

On April 26, 2023, the EC submitted a proposal for the reform of the European pharmaceutical legislation.

The current draft envisages e.g., a shortening of the periods of data exclusivity, however, there is currently neither a final version of this draft nor a date for its entry into force.

While the European Parliament adopted its approving position on the reform on April 10, 2024, no further required legislative steps have been taken since.

On April 26, 2023, the EC submitted a proposal for the reform of the European pharmaceutical legislation and negotiations are still ongoing.

The timing for finalization of these negotiations and entry into force are unclear.

The current drafts envisage:

• a shortening of the periods of data exclusivity from eight to six years(with transferable vouchers for an additional year of market protection as an incentive for the development of new antibiotics);

• earlier regulatory guidance and extension of market exclusivity for orphan medicines (depending on certain conditions);

• four-year data exclusivity for additional indications of existing products;

• rules governing the availability of products (including shortage prevention plans and some supply obligations for manufacturers).

Orphan Designation and Exclusivity

22 unchanged sentences

Overall, the requirements for orphan designation largely replicate the requirements in the EU and the benefit of market exclusivity has been retained.

Products with an orphan designation in the EU can be considered for an orphan MA in Great Britain, but a UK-wide orphan MA can only be considered in the absence of an active EU orphan designation.

Products with an orphan designation in the EU can be considered for an orphan MA in Great Britain and, marketing authorizations granted for products that fulfil UK orphan criteria are valid UK-wide regardless of whether there is an EU orphan designation.

The MHRA will review applications for orphan designation at the time of a MA, and will offer incentives, such as market exclusivity and full or partial refunds for MA fees to encourage the development of medicines in rare diseases.

Separately, the MHRA has stated that it is considering updating its licensing framework for orphan medicines, with a draft framework expected by spring 2026.

Pediatric Development

8 unchanged sentences

An approved PIP is also required when a MA holder wants to add a new indication, medicinal form or route of administration for a medicine that is already authorized and covered by intellectual property rights.

In the UK, the MHRA has published guidance on the procedures for UK Paediatric Investigation Plans (“PIPs”) which, where possible, mirror the submission format and requirements of the EU system.

EU PIPs remain applicable for Northern Ireland and EU PIPs agreed by the EMA prior to January 1, 2021 have been adopted as UK PIPs.

In the UK, the MHRA has published guidance on the procedures for UK PIPs which, where possible, mirror the submission format and requirements of the EU system.

From January 1, 2025, EU pediatric requirements are addressed via Windsor Framework categorization:

for Category 2 products, both UK and EU pediatric requirements apply, and an EU-agreed PIP must also be in place (unless waived).

PRIME Designation

11 unchanged sentences

Failure by us or by any of our third-party partners, including suppliers, manufacturers and distributors to comply with EU laws and the related national laws of individual EU Member States governing the conduct of clinical trials, manufacturing approval, MA of medicinal products and marketing of such products, both before and after grant of MA, statutory health insurance, bribery and anti-corruption or other applicable regulatory requirements may result in administrative, civil or criminal penalties.

These penalties could include delays or refusal to authorize the conduct of clinical trials or to grant MA, product withdrawals and recalls, product seizures, suspension, withdrawal or variation of the MA, total or partial suspension of production, distribution, manufacturing or clinical trials, operating restrictions, injunctions, suspension of licenses, fines and criminal penalties.

These penalties could include delays or refusal to authorize the conduct of clinical trials or to grant MA, product withdrawals and recalls, product seizures, suspension, withdrawal or variation

of the MA, total or partial suspension of production, distribution, manufacturing or clinical trials, operating restrictions, injunctions, suspension of licenses, fines and criminal penalties.

The holder of a MA for a medicinal product must also comply with EU pharmacovigilance legislation and its related regulations and guidelines, which entail many requirements for conducting pharmacovigilance, or the assessment and monitoring of the safety of medicinal products.

1 unchanged sentence

MA holders must establish and maintain a pharmacovigilance system and appoint an individual qualified person for pharmacovigilance, who is responsible for oversight of that system.

Key obligations include expedited reporting of suspected serious adverse reactions and submission of PSURs in relation to medicinal products for which they hold MAs.

Key obligations include expedited reporting of suspected serious adverse reactions and submission of Periodic Safety Update Reports (“PSURs”) in relation to medicinal products for which they hold MAs.

The EMA reviews PSURs for medicinal products authorized through the centralized procedure.

11 unchanged sentences

Manufacturing facilities are subject to periodic inspections by the competent authorities for compliance with GMP.

On October 27, 2025, the Council of the European Union approved a framework for compulsory licensing of crisis-relevant products (including medicinal products) in crisis situations.

While the proposal focuses on voluntary agreements with intellectual property rights holders, it includes rules on compulsory licensing as a measure of last resort upon activation / declaration of a crisis or emergency mode.

The European Parliament has not yet voted on the proposal.

Sales and Marketing Regulations

1 unchanged sentence

In addition, other national legislation of individual EU Member States may apply to the advertising and promotion of medicinal products and may differ from one country to another.

These laws require that promotional materials and advertising in relation to medicinal products comply with the product’s SmPC as approved by the competent regulatory authorities.

These laws require that promotional materials and advertising in relation to medicinal products comply with the product’s SmPC as approved by the competent

regulatory authorities.

The SmPC is the document that provides information to physicians concerning the safe and effective use of the medicinal product.

5 unchanged sentences

These laws may further limit or restrict the advertising and promotion of our products to the general public and may also impose limitations on its promotional activities with healthcare professionals.

EU regulation with regards to dispensing, sale and purchase of medicines has generally been preserved in the UK following Brexit, through the HMRs.

EU regulation with regards to dispensing, sale and purchase of medicines has generally been preserved in the UK following Brexit, through the Hazardous Material Regulations.

However, organizations wishing to sell medicines online need to register with the MHRA.

39 unchanged sentences

Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business