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Item 1. Business

2026-03-16 compared with 2025-03-11 · 567 added, 400 removed, 976 unchanged (50% of the section changed)

We are a clinical stage global biopharmaceutical company committed to being a leader in the development and commercialization of transformative immunology-based therapies for patients in need.

With the evolving understanding of the pathogenesis of autoimmune diseases, along with the expansion of promising immunology-based pharmacologic targets, we are building an immunology and inflammation (“I&I”) focused biopharmaceutical company.

With the evolving understanding

of the pathogenesis of autoimmune diseases, along with the expansion of promising immunology-based pharmacologic targets, we are building an I&I focused biopharmaceutical company.

Our core business strategy combines disciplined product candidate acquisition with strategic deployment of internal expertise and effective use of external resources.

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We believe obexelimab’s mechanism of action and chronic dosing regimen may broadly and effectively address the pathogenic role of B cell lineage in chronic autoimmune disease.

Across five clinical trials, in which 198 subjects were dosed, obexelimab was well-tolerated and demonstrated clinical activity that we believe provides POC for obexelimab as a B cell inhibitor for the treatment of patients living with certain autoimmune diseases and, together with its mechanism of action, positions obexelimab to be a potentially differentiated B cell therapy for the treatment of such patients.

Across eight clinical trials, including INDIGO and MoonStone, in which 383 subjects were dosed, obexelimab was well-tolerated and demonstrated clinical activity that we believe provides POC for obexelimab as a B cell inhibitor for the treatment of patients living with certain autoimmune diseases and, together with its mechanism of action, positions obexelimab to be a potentially differentiated B cell therapy for the treatment of such patients.

We believe obexelimab holds the potential to provide meaningful clinical benefit for patients in multiple I&I indications.

We are developing obexelimab as a potential I&I franchise for patients in several autoimmune diseases, representing substantial commercial opportunities, individually and in the aggregate.

The first three indications we are pursuing include immunoglobulin G4-related disease (“IgG4-RD”) through an ongoing registration-directed Phase 3 trial which completed enrollment in November 2024 and relapsing multiple sclerosis (“RMS”) and systemic lupus erythematosus (“SLE”) through ongoing Phase 2, double-blind, randomized, placebo-controlled trials, each of which are currently enrolling.

The first three indications we are pursuing include immunoglobulin G4-related disease (“IgG4-RD”) through a registration-directed Phase 3 trial which reported topline data in January 2026, and relapsing multiple sclerosis (“RMS”), through a Phase 2, double-blind, randomized, placebo-controlled trial which reported topline data in October 2025, and systemic lupus erythematosus (“SLE”) through an ongoing Phase 2, double-blind, randomized, placebo-controlled trial for which we expect to report topline results, including biomarker data, in the fourth quarter of 2026.

We estimate that each of these potential indications represent a multi-billion-dollar commercial opportunity in the U.S.

Beyond our lead product candidate, obexelimab, we have two other programs for the potential treatment of other I&I indications that we may continue to advance and ultimately develop and commercialize with partners.

In January 2026, we reported positive results from the Phase 3 trial of obexelimab in patients with IgG4-RD (the “INDIGO”) trial.

Obexelimab met the primary endpoint, demonstrating a highly statistically significant and clinically meaningful 56% reduction in the risk of IgG4-RD flare compared to placebo (Hazard Ratio 0.44, p=0.0005) and also met and demonstrated highly statistically significant activity compared to placebo on all four key secondary endpoints.

Obexelimab was well tolerated with a safety profile consistent with that observed in previously completed clinical trials.

Based on these results, we plan to submit the obexelimab Biologics License Application (“BLA”) to the U.S.

Food and Drug Administration (“FDA”) for the treatment of IgG4-RD in the second quarter of 2026.

We also intend to submit a Marketing Authorization Application (“MAA”) to the European Medicines Agency (“EMA”) in the second half of 2026.

In October 2025, we reported that the Phase 2 trial for RMS (“MoonStone”) met its 12-week primary endpoint, demonstrating a highly statistically significant 95% relative reduction in the cumulative number of new gadolinium-enhancing (“GdE”) T1 hyperintense lesions over week 8 and week 12 compared with placebo (p=0.0009).

In February 2026, we reported the 24-week data from MoonStone trial which confirmed the reductions in total GdE T1 hyperintense lesions observed with obexelimab over weeks 8 and 12 were maintained through week 24;

unadjusted mean numbers of new lesions per scan were 0.87 at baseline, 0.08 at week 12 and 0.04 at week 24 for obexelimab indicating a 95% reduction.

In addition to obexelimab, we are developing orelabrutinib, a Bruton’s Tyrosine Kinase inhibitor (“BTK”), for progressive forms of multiple sclerosis.

Orelabrutinib is a highly selective and central nervous system (“CNS”)-penetrant, oral small molecule BTK inhibitor.

Orelabrutinib is designed to bind irreversibly to BTK with minimal off-target effects, which may potentially reduce certain side effects.

We believe orelabrutinib is designed to efficiently cross the blood-brain barrier, reaching therapeutic levels within the CNS to directly target inflammation in diseases like Multiple Sclerosis (“MS”).

We are advancing orelabrutinib in a global, Phase 3, multicenter, randomized, double-blind, placebo-controlled clinical trial in patients with Primary Progressive Multiple Sclerosis (“PPMS”), the (“PriMroSe”) trial, and we plan to initiate a second global, Phase 3, multicenter, randomized, double-blind, placebo-controlled clinical trial evaluating orelabrutinib in patients with non-active Secondary Progressive Multiple Sclerosis (“non active SPMS”), the (“Monarch”) trial in the first quarter of 2026.

We also have two early-development product candidates:

ZB021 and ZB022.

ZB021 is an oral IL-17AA/AF inhibitor designed to block both IL-17AA homodimer and IL-17AF heterodimer signaling.

We expect Phase 1 clinical study initiation in 2026.

ZB022 is an oral, brain-penetrant tyrosine kinase 2 (“TYK2”)-JH2 inhibitor, currently in Investigational New Drug (“IND”)-enabling studies.

Subject to the results of the IND-enabling studies, we expect to submit an IND application for ZB022, and if cleared, initiate a Phase 1 clinical study in 2026.

In addition, we have two other programs for the potential treatment of other I&I indications that we may continue to advance and ultimately commercialize with partners.

These consist of ZB002 (an anti-TNFα monoclonal antibody) and ZB004 (a CTLA-4-Ig fusion).

We retain global rights for both assets.

In addition, we hold the development and commercialization rights to one regional program, ZB001 (also known as VRDN-001, an insulin-like growth factor-1 receptor (“IGF-1R”) monoclonal antibody and related programs, which were recently exclusively sublicensed to a partner in greater China.

In addition, we hold the development and commercialization rights to one regional program, ZB001 (also known as VRDN-001, an insulin-like growth factor-1 receptor (“IGF-1R”) monoclonal antibody and related programs, which were exclusively sublicensed to a partner in greater China.

To date, we have no product candidates approved for commercial sale in any country and have not generated any revenue from product sales.

We are developing obexelimab, orelabrutinib and other product candidates for the treatment of several I&I diseases summarized in the pipeline figure below:

Bristol Myers Squibb & Co.

holds exclusive development and commercialization rights for obexelimab in Japan, South Korea, Taiwan, Hong Kong, Singapore, Australia.

InnoCare territories

Obexelimab Overview

We are developing obexelimab for the treatment of several I&I diseases summarized in the pipeline figure below:

Our lead product candidate, obexelimab, was engineered to mimic the natural antigen-antibody complex for the inhibition of B cells.

Obexelimab was engineered to mimic the natural antigen-antibody complex for the inhibition of B cells.

By targeting CD19, obexelimab is designed to inhibit a broader B cell population, including plasmablasts and the subpopulation of CD19 expressing plasma cells, each of which produces high amounts of auto-antibodies.

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In addition, obexelimab is designed to inhibit rather than destroy or deplete B cell lineage.

Other anti-CD19 and CD20 targeting antibodies rely on antibody-dependent cell-mediated cytotoxicity (“ADCC”), complement-dependent cytotoxicity (“CDC”) and/or apoptosis or programmed cell death as a key component of their mechanism of action.

Other anti-CD19 and CD20 targeting antibodies rely on antibody-dependent cell-

mediated cytotoxicity (“ADCC”), complement-dependent cytotoxicity (“CDC”) and/or apoptosis or programmed cell death as a key component of their mechanism of action.

ADCC, CDC and apoptosis activity are generally lower in disease-relevant tissue than the peripheral blood.

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We believe the rapid return in B cell activity following the cessation or pause in obexelimab dosing could allow the patient’s immune system to more quickly return to baseline to protect against infections and allow a patient to receive vaccinations within as few as six weeks of his or her last dose, rather than potentially waiting six months or longer following treatment with an anti-CD19 or anti-CD20 targeted depleting therapy.

Obexelimab has been evaluated in five completed clinical trials in which a total of 198 subjects have received obexelimab either as IV infusion at doses of up to 10 mg/kg (n=158) or as a SC injection at doses of up to 375 mg (n=40).

Obexelimab was well-tolerated across these five trials and demonstrated PK, as well as clinical activity providing POC in multiple I&I

Obexelimab has been evaluated in eight clinical trials in which a total of 383 subjects have received obexelimab either as IV infusion (n=158) or as a subcutaneous (“SC”) injection (n=225).

Obexelimab was well-tolerated across these eight trials and demonstrated PK, as well as clinical activity providing POC in multiple I&I indications.

Based on this clinical data, we believe obexelimab could have potential advantages over anti-CD19 and -CD20 targeted depleting agents.

We are also developing ZB014, an anti-CD-19 and FcγRIIb monoclonal antibody designed to extend half-life, which is currently being evaluated in pre-clinical studies.

Orelabrutinib Overview

Orelabrutinib, also known as ZB020, is a highly selective and CNS-penetrant, oral small molecule BTK inhibitor.

Orelabrutinib is designed to bind irreversibly to BTK with minimal off-target effects, compared to certain other BTK inhibitors, which may potentially reduce certain side effects.

We believe orelabrutinib is designed to efficiently cross the blood-brain barrier, reaching therapeutic levels within the CNS to directly target inflammation in diseases like MS.

This CNS penetration may be important for addressing the underlying disease pathology of progressive forms of MS, which is characterized by compartmentalized neuroinflammation and neurodegeneration.

The mechanism of action of BTK inhibitors targets not only pathogenic B cells in the periphery, but also those in the CNS, as well as macrophages and microglial cells addressing the key pathogenic drivers of progressive MS.

Early-Development Product Candidates:

ZB021 and ZB022

ZB021 is an oral small molecule IL-17AA/AF inhibitor designed to block both IL-17AA homodimer and IL-17AF heterodimer signaling, ZB022 is an oral small molecule, brain-penetrant TYK2-JH2 inhibitor.

Preclinical studies for ZB021 have shown favorable PK and ADME properties.

ZB021 achieved comparable activity in vivo to a reference anti-IL-17 biologic in a rat collagen-induced arthritis (“CIA”) model.

We expect Phase 1 clinical study initiation in 2026, with the potential for initial data in patients in 2027.

ZB022 is currently in IND-enabling studies.

Subject to the results of IND-enabling studies, we expect to submit an IND application for ZB022, and, if cleared, initiate a Phase 1 clinical study in 2026, with the potential for initial data in 2027

Other Programs

Product Candidate

Plan of Development

ZB002 (anti-TNFα mAb)

Phase 1b multiple ascending dose ("MAD") study in patients with RA ongoing

ZB004 (CTLA-4-Ig fusion)

Phase 1 single ascending dose ("SAD") study in healthy volunteers completed

ZB002, an anti-TNFα therapy designed to have an extended half-life as compared to existing anti-TNFα therapies.

ZB002 is a recombinant human monoclonal antibody directed at human TNFα.

ZB002 has an identical amino acid sequence to Humira (adalimumab) in the TNFα-binding region of the fragment variable domain;

however, the Fc domain of ZB002 contains modifications designed to extend its half-life in vivo .

If the results of our ongoing Phase 1b MAD study of ZB002 are favorable, we may seek to identify a partner to advance ZB002 in subsequent trials for potential use as a treatment for certain I&I diseases that can benefit from TNFα inhibition.

We also own the global development and commercialization rights to ZB004, a CTLA-4-Ig fusion protein designed to have an extended half-life compared to approved CTLA-4-Ig fusion protein therapies, such as Orencia (abatacept) and Nulojix (belatacept).

Similar to approved CTLA-4-Ig fusion protein therapies, the ZB004 mechanism of action is selective inhibition of T cell co-stimulation.

The CTLA-4 motif binds to CD80 and CD86 on antigen-presenting cells, blocking the interaction of these receptors with CD28 on T lymphocytes, and thus inhibiting T cell co-stimulation.

ZB004 contains two CTLA-4 extracellular domain substitutions designed to potentially produce greater CD80 and CD86 binding.

Based on the ongoing analysis of data from the Phase 1 study, along with the known clinical efficacy of approved CTLA-4-Ig fusion protein therapies, we are seeking to advance the clinical development of ZB004 with a potential partner in indications where it could be uniquely positioned given its profile.

In addition, we have two other programs for the potential treatment of other I&I indications that we may continue to advance and ultimately develop and commercialize with partners.

These include ZB002, an anti-TNFα therapy designed to have an extended half-life as compared to existing anti-TNFα therapies and ZB004, a CTLA-4-Ig fusion protein designed to have an extended half-life compared to approved CTLA-4-Ig fusion protein therapies.

Partnered Regional Programs

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(“Viridian”) in China, Hong Kong, Macau and Taiwan (collectively, “greater China”).

On January 24, 2025, we entered into a license agreement (the “Zai License Agreement”) with Zai Lab (Hong Kong) Limited (“Zai”), under which we granted Zai an exclusive sublicense to develop and commercialize ZB001 and related programs in greater China.

As partial consideration for the Zai License Agreement, we received an upfront fee of $10.0 million from Zai.

In addition, we are eligible to receive up to $96.0 million upon the achievement of certain future development and commercial milestones and royalty percentage rates from the low to mid-single digits, net of pass-through obligations due to Viridian.

In addition, on October 21, 2024, we entered into a novation agreement with Tenacia Biotechnology (Hong Kong) Co., Limited (“Tenacia”), under which we transferred to Tenacia our rights and obligations under our agreements with Dianthus Therapeutics Inc.

In January 2025, we entered into a license agreement (the “Zai License Agreement”) with Zai Lab (Hong Kong) Limited (“Zai”), under which we granted Zai an exclusive sublicense to develop and commercialize ZB001 and related programs in greater China.

In addition, in October 2024, we entered into a novation agreement with Tenacia Biotechnology (Hong Kong) Co., Limited (“Tenacia”), under which we transferred to Tenacia our rights and obligations under our agreements with Dianthus Therapeutics Inc.

(“Dianthus”) for ZB005 (the “Tenacia Agreement”).

As partial consideration for the Tenacia Agreement, we received an upfront fee of $5.0 million from Tenacia.

In addition, we are eligible to receive up to $86.0 million upon the achievement of certain future regulatory and commercial milestones.

Our Management Team

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Moulder co-founded TESARO, an oncology-focused biopharmaceutical company, serving as Chief Executive Officer and Director until its acquisition by GlaxoSmithKline.

He previously served as President and Chief

Executive Officer of Abraxis BioScience and as Vice Chairman of Eisai Corporation of North America following Eisai’s acquisition of MGI PHARMA, where he served as President and Chief Executive Officer.

Moulder is joined by our team of veteran biopharmaceutical executives, including Joseph Farmer, Jennifer Fox and Orlando Oliveira, who together with the leadership team, bring exceptional track records and experiences across the industry at companies such as TESARO, Inc., GlaxoSmithKline plc., Amgen Inc., Nuvation Bio Inc., Mirati Therapeutics, Inc., Cubist Pharmaceuticals, Inc.

and other biopharmaceutical companies.

He previously served as President and Chief Executive Officer of Abraxis BioScience and as Vice Chairman of Eisai Corporation of North America following Eisai’s acquisition of MGI PHARMA, where he served as President and Chief Executive Officer.

Moulder is joined by our team of veteran biopharmaceutical executives, including Joseph Farmer, Jennifer Fox, and Lisa von Molkte, M.D., who together with the leadership team, bring exceptional track records and experiences across the industry at companies such as TESARO, Inc., GlaxoSmithKline plc., Amgen Inc., Nuvation Bio Inc., Cubist Pharmaceuticals, Inc., Seres Therapeutics and other biopharmaceutical companies.

Our leadership team has collectively been responsible for numerous INDs, and NDAs/BLAs and the associated commercial product launches of several successful pharmaceutical products.

Our vision is to become a global leader in delivering transformative I&I therapeutics to patients in need.

We intend to leverage the experience and capabilities of our executive management team and our established networks throughout the biopharmaceutical industry to identify, acquire, develop and, if approved, commercialize product candidates that we believe can offer enhanced efficacy, safety and/or convenience over existing therapies and thereby provide superior benefits to patients.

believe can offer enhanced efficacy, safety and/or convenience over existing therapies and thereby provide superior benefits to patients.

We intend to achieve our goals by implementing the following strategies:

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We are developing obexelimab as a potential I&I franchise for patients in several autoimmune diseases, representing substantial commercial opportunities individually and in the aggregate.

The first three indications we are pursuing include IgG4-RD through an ongoing registration-directed Phase 3 trial;

The first three indications we are pursuing include IgG4-RD through a successful registration-directed Phase 3 trial;

and RMS and SLE through ongoing Phase 2, double-blind, randomized, placebo-controlled trials.

● Build our operational capabilities to develop and potentially commercialize our products in key regions.

With plans to advance our obexelimab franchise in multiple I&I indications, we intend to build the commercial capabilities necessary to achieve our goal of becoming a global development and commercial stage biopharma company.

To that end, we have hired a Chief Commercial Officer and others within the commercial organization.

● Utilize our business development experience and expertise to continue to build a deep and balanced portfolio of products and product candidates.

With plans to advance our obexelimab franchise in multiple I&I indications, we are building the commercial capabilities necessary to achieve our goal of becoming a global development and commercial stage biopharma company.

● Utilize our business development experience and expertise to maintain a deep and balanced portfolio of products and product candidates.

We acquired each of our product candidates through in-licensing from third parties.

We intend to continue to utilize our business development strategy and expertise to build a balanced portfolio of new product candidates from preclinical through commercial assets.

In October 2025, we licensed the exclusive rights to develop and commercialize orelabrutinib in MS worldwide and across all therapeutic areas other than oncology, worldwide, excluding greater China and Southeast Asia.

As part of this transaction, we also secured rights to a novel, oral IL-17AA/AF inhibitor, and an oral, brain-penetrant, TYK2 inhibitor.

We intend to continue to utilize our business development strategy and expertise to maintain a balanced portfolio of new product candidates from preclinical through commercial assets.

● Leverage success with initial indications to expand into broader I&I opportunities.

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In addition, for certain indications that may require larger clinical development programs, we may selectively seek to collaborate to help fund development.

Obexelimab (CD19 x FcγRIIb bifunctional monoclonal antibody) Program

We believe that our lead product candidate, obexelimab, has the potential to address key unmet needs in multiple I&I indications due to its mechanism of action and chronic dosing regimen that may broadly and effectively address the pathogenic role of B cell lineage through reversible inhibition of B cell activity without causing B cell depletion.

Obexelimab is a bifunctional, non-depleting, humanized monoclonal antibody designed to bind CD19 and FcγRIIb to inhibit B-lineage cell activity.

Obexelimab (CD19 and FcγRIIb bifunctional monoclonal antibody) Program

We believe that obexelimab has the potential to address key unmet needs in multiple I&I indications due to its mechanism of action and chronic dosing regimen that may broadly and effectively address the pathogenic role of B cell lineage through reversible inhibition of B cell activity without causing B cell depletion.

Obexelimab is a bifunctional, humanized monoclonal antibody designed to bind CD19 and FcγRIIb to inhibit B-lineage cell activity.

The antibody variable region of obexelimab has been engineered to bind CD19, whereas the constant region has been engineered to enhance affinity for the inhibitory FcγRIIb receptor.

FcγRIIb is the only Fc receptor on B cells and serves as an antibody-sensing down-regulator of humoral immunity that is naturally engaged by

immune complexes.

FcγRIIb is the only Fc receptor on B cells and serves as an antibody-sensing down-regulator of humoral immunity that is naturally engaged by antigen-antibody complexes.

In addition, FcγRIIb regulates the activity of other B cell stimulators including interleukin-4, lipopolysaccharide and B cell activating factor (“BAFF”) that amplify BCR-driven proliferation and differentiation.

By binding CD19 and FcγRIIb, obexelimab mimics the action of naturally occurring antigen-antibody complexes and inhibits B cell activity without depleting B cells in the lymph nodes or spleen.

By binding CD19 and FcγRIIb, obexelimab mimics the action of naturally occurring antigen-antibody complexes and inhibits B cell activity without depleting B cells through ADCC and CDC.

The mechanism of action of obexelimab shown below in Figure 1, involves co-engagement of CD19 and FcγRIIb, leading to inhibition of B cell activity, including antibody production, proliferation, cytokine secretion, B cell differentiation, and antigen presentation to T cells.

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Clinical Development

Obexelimab has been evaluated in five completed clinical trials in which a total of 198 subjects have received obexelimab either as an IV infusion at doses of up to 10 mg/kg (n=158) or as a SC injection at doses up to 375 mg (n=40).

Across these five trials obexelimab was well-tolerated and demonstrated clinical activity that we believe provides POC for obexelimab as a B cell inhibitor for the treatment of patients living with certain autoimmune diseases.

Obexelimab has been evaluated in eight clinical trials, including INDIGO and MoonStone, in which a total of 383 subjects have received obexelimab either as an IV infusion (n=158) or as a SC injection (n=225).

Across these eight trials obexelimab was well-tolerated and demonstrated clinical activity that we believe provides POC for obexelimab as a B cell inhibitor for the treatment of patients living with certain autoimmune diseases.

Our current ongoing and planned future trials of obexelimab utilize a fixed 250 mg, dosed weekly as a self-administered SC injection.

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Established bridging of IV to SC formulation

SApHiAre Trial

Demonstrated proof of mechanism in patients with warm autoimmune hemolytic anemia (wAIHA)

* These clinical studies were conducted by Xencor.

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● Study in Healthy Adult Volunteers:

XmAb5871-01 was a Phase 1, randomized, blinded, placebo-controlled, SAD IV study of the safety, tolerability and PK of obexelimab in 48 healthy adult volunteers, with 36 receiving study drug, conducted in the United Kingdom.

XmAb5871-01 was a Phase 1, randomized, blinded, placebo-controlled, SAD IV study of the safety, tolerability and pharmacokinetics (“PK”) of obexelimab in 48 healthy adult volunteers, with 36 receiving study drug, conducted in the United Kingdom.

The primary objective of the study was to evaluate the safety and tolerability profile of a single-dose IV administration of obexelimab.

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The study demonstrated that obexelimab was well tolerated at all doses, including the highest dose of 10 mg/kg.

Gastrointestinal (“GI”)-related TEAE (including nausea, vomiting, abdominal pain, abdominal discomfort, epigastric discomfort and diarrhea) were the most frequently reported (14/36, 38.9%).

There were no SAEs reported.

Gastrointestinal (“GI”)-related treatment emergent adverse events (“TEAE”) (including nausea, vomiting, abdominal pain, abdominal discomfort, epigastric discomfort and diarrhea) were the most frequently reported (14/36, 38.9%).

There were no serious adverse events (“SAEs”) reported.

The study was not powered for statistical significance.

● Trial in Rheumatoid Arthritis:

XmAb5871-02 was a Phase 1b/2a, randomized, placebo-controlled, double-blind, ascending multiple-IV dose trial of the safety, tolerability, PK, and PD of obexelimab in 56 patients with RA, with 40 receiving study drug.

The trial was conducted at nine sites in four countries, including, Hungary, Poland, Czech Republic and Slovakia.

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XmAb5871-03 was a Phase 2, open-label, single-arm IV, trial in 20 patients with IgG4-RD, including 15 patients dosed with 5 mg/kg of obexelimab, conducted in Boston, Massachusetts.

The primary objective of the trial was to evaluate the effect of every-other-week IV administration of obexelimab on the IgG4-RD Responder Index (“RI”).

The primary objective of the trial was to evaluate the effect of every-other-week IV administration of obexelimab on the IgG4-

RD Responder Index (“RI”).

The secondary objectives were to (i) evaluate the safety and tolerability of every-other-week IV administration of obexelimab in subjects with active IgG4-RD and (ii) evaluate the PK and immunogenicity of every-other-week IV administration of obexelimab in subjects with active IgG4-RD.

primary efficacy analysis, in patients receiving 5 mg/kg, the IgG4-related disease RI score at Day 169 had decreased by two or more points versus baseline in 12 (80%) patients, eight (67%) of whom had a score of zero (complete remission).

In the primary efficacy analysis, in patients receiving 5 mg/kg, the IgG4-related disease RI score at Day 169 had decreased by two or more points versus baseline in 12 (80%) patients, eight (67%) of whom had a score of zero (complete remission).

Fourteen (93%) patients achieved an improvement on the RI of two or more points during at least one trial assessment at a median of 15 days (range 14 to 90) from treatment initiation.

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Obexelimab has demonstrated clinical activity across multiple I&I indications.

We are currently pursuing a registration-directed trial in patients with IgG4-RD and ongoing Phase 2, double-blind, randomized, placebo-controlled clinical trials of obexelimab in patients with RMS and SLE.

As described below, we recently announced positive topline data in a registration-directed Phase 3 trial in patients with IgG4-RD and are currently pursuing ongoing

Phase 2, double-blind, randomized, placebo-controlled clinical trials of obexelimab in patients with RMS and SLE.

Despite the promising results from the Phase 1b/2a trial of obexelimab in RA, we do not intend to develop obexelimab further in RA due to the competitive landscape in that disease.

While we believe that the preliminary results from the SApHiAre Trial in patients with warm autoimmune hemolytic anemia

(“wAIHA”) patients established proof of mechanism through an increase in Hgb and a positive effect on other clinical markers, we have determined not to progress to a registration-directed trial of obexelimab for the wAIHA indication based on several factors, including the expected length and expense of a potential Phase 3 trial.

While we believe that the results from the SApHiAre Trial in patients with warm autoimmune hemolytic anemia (“wAIHA”) patients established proof of mechanism through an increase in Hgb and a positive effect on other clinical markers, we have determined not to progress to a registration-directed trial of obexelimab for the wAIHA indication based on several factors, including the expected length and expense of a potential Phase 3 trial.

Obexelimab for the Treatment of IgG4-RD

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The reported evidence for the role of B cells in the pathogenesis of IgG4-RD, the observed effects of B cell targeting agents in previous trials in IgG4-RD and the data from our Phase 2 IgG4-RD trial with obexelimab support the continued development of obexelimab in patients with IgG4-RD.

In November 2024, we completed enrollment of in our INDIGO Trial, a global Phase 3 registration-directed, randomized, double-blind placebo-controlled trial of obexelimab delivered 250 mg subcutaneously weekly to evaluate the prevention of flares in patients with IgG4-RD.

We expect to report topline data from our INDIGO Trial year end 2025 and, subject to the data, submit a biologics license application (“BLA”) in 2026.

In January 2026, we reported positive results from the Phase 3 trial of obexelimab in patients with IgG4-RD (the “INDIGO” trial).

Obexelimab was well tolerated with a safety profile consistent with that observed in previously completed clinical trials.

Based on these results, we plan to submit the obexelimab BLA to the FDA for the treatment of IgG4-RD in the second quarter of 2026.

We also intend to submit an MAA to the EMA in the second half of 2026.

IgG4-RD Histology and Disease Background

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Current Treatment and Unmet Need

Despite the growing recognition of IgG4-RD and advances in the understanding of its pathophysiology, there are no approved therapies for the treatment of this disease and there remains high unmet medical need.

Despite the growing recognition of IgG4-RD and advances in the understanding of its pathophysiology, there is only one approved therapy for the treatment of this disease and there remains high unmet medical need.

There are few treatment options, which are often limited by co-morbidities common among patients with IgG4-RD, including diabetes, obesity and hypertension.

The current standard of care is glucocorticoid treatment (“GCs”), however such treatment often results in various complications.

Glucocorticoid (“GC”) treatment is commonly used, however such treatment often results in various complications.

Although GCs are initially effective in most patients, up to 60% of patients with IgG4-RD will relapse within 12 months of discontinuing GC treatment.

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As a result, although not approved by any regulatory bodies to treat IgG4-RD, certain B cell depleting agents (e.g.

rituximab) are occasionally used in such patients.

rituximab) are occasionally used in such patients, and in April 2025, inebilizumab, a B cell depleting agent, was approved by the FDA.

However, B cell depleting agents are often associated with infections, including serious opportunistic infections, and can compromise a patient’s ability to mount a response to vaccinations.

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We believe this is due to the fact that rituximab and other B cell depleting agents can cause prolonged depletion of B cells for six months or longer, which places patients at risk of opportunistic infections and potentially reduces response to vaccines.

INDIGO Trial—Our Global Phase 3 Trial in IgG4-RD

In January 2026, we announced positive results from the INDIGO trial.

The INDIGO trial enrolled a total of 194 patients, randomized to obexelimab (n=97) and placebo (n=97).

Obexelimab met the primary endpoint, demonstrating a

highly statistically significant 56% reduction in the risk of IgG4-RD flare that requires initiation of a rescue therapy compared to placebo (Hazard Ratio 0.443, p=0.0005) during the 52-week randomized placebo-controlled period.

The number of participants with flares was 26 (26.8%) in the obexelimab arm and 53 (54.6%) in the placebo arm.

Obexelimab also met and demonstrated highly statistically significant activity compared to placebo with respect to all four key secondary endpoints, which were time to first investigator-determined IgG4-RD flare requiring initiation of rescue therapy (p=0.0001), the number of flares requiring initiation of rescue therapy (p=0.0008), the proportion of patients achieving complete remission (p=0.0049) and the cumulative use of IgG4-RD glucocorticoid rescue therapy (p=0.0042).

Obexelimab was well tolerated with a safety profile consistent with that observed in previously completed clinical trials.

When compared to the placebo arm, incidences of serious adverse events were lower in the obexelimab arm (obexelimab 10% vs.

placebo 19%).

Additionally, overall rates of infections, including Grade 3, were lower in the obexelimab arm compared to placebo (Grade 3 infections, obexelimab 2% vs.

placebo 4%), as well as related upper respiratory tract infections (obexelimab 5% vs.

Lower rates of urinary tract infections and rates of COVID-19 were observed with obexelimab compared to placebo (obexelimab 2% vs placebo 4%).

Percentage of doses with injection site reactions were similar across both study arms (obexelimab 3.5% vs.

placebo 2.3%).

Three malignancies were identified (all deemed unrelated):

one renal cell carcinoma determined to be pre-existing before enrollment;

one prostate cancer, for which there is no known increased risk with immunosuppression;

and one squamous cell carcinoma.

Following the positive Phase 3 INDIGO results, we anticipate submitting a BLA to the FDA for obexelimab in IgG4-RD in the second quarter of 2026.

We also intend to submit an MAA to the EMA in the second half of 2026.

INDIGO Trial Overview

The INDIGO Trial is a global Phase 3 registration-directed, double-blind, placebo-controlled trial to evaluate the safety and efficacy of SC obexelimab in patients with active IgG4-RD in a randomized controlled period followed by an optional open-label extension period.

Approximately 190 patients were enrolled in the randomized control period (“RCP”) and all patients from the RCP are eligible for the open label extension (“OLE”) period.

The trial is being conducted at approximately 100 sites in 20 countries.

The RCP consists of a screening period (Day -28 to Day -1) and a 52-week treatment period, during which 250 mg of obexelimab or placebo were administered as an SC injection every seven days.

Following the 52-week RCP, eligible patients had the opportunity to continue in an OLE period where all patients will receive obexelimab.

INDIGO Trial Schema

To be considered eligible for the screening period, patients must have had a clinical diagnosis of IgG4-RD, met the 2019 ACR/EULAR classification criteria for IgG4-RD, as determined by an Adjudication Committee (“AC”), and had active IgG4-RD signs/symptoms (i.e., flare) that require, as assessed by the investigator, the initiation of GC therapy or an increase in background long-term GC therapy.

All patients were required to receive three to six weeks of GC treatment at a dose of 20 to 60 mg/day prednisone equivalent prior to randomization.

The required GC therapy could either have been newly initiated or an increase in long-term GC therapy (i.e., patient was previously on a dose of ≤ 10 mg/day prednisone equivalent).

The exact dose and taper schedule during the screening period and prior to randomization are at the discretion of the investigator.

However, on the day of randomization, patients must have had no disease activity and been at a dose of 20 mg/day prednisone equivalent.

Patients were randomized 1:1 to receive obexelimab or placebo.

The primary efficacy assessment was time to first IgG4-RD flare, as determined by the investigator and the AC.

biochemical parameters specific to the involved organ(s), to correlate symptoms and to document disease activity.

The investigator then determined if an IgG4-RD flare occurred and whether the initiation of rescue therapy was required.

The AC independently reviewed these diagnostic assessments to determine if, in their judgement, the signs/symptoms represent a flare.

Patients who met the protocol-defined criteria for IgG4-RD flare, by both the investigator and the AC, were counted as treatment failures for the primary endpoint of time to first flare and the key secondary endpoint of proportion of patients who remain free of IgG4-RD flare (i.e., complete remission).

Rescue therapy outside of permitted GC therapy would result in discontinuation from obexelimab or placebo treatment, as the case may be.

The trial was designed with approximately 90% power to detect a hazard ratio of 0.376 using a one-sided log-rank test at a significance level equal to 0.025.

Summary of the Completed Phase 2 Trial of Obexelimab in IgG4-RD

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Fourteen (93%) patients achieved an improvement on the RI of two or more points during at least one trial assessment at a median of 15 days (range 14 to 90) from treatment initiation.

One (7%) patient did not achieve an improvement on the RI score of two or more points, and further evaluation found that this patient who failed to achieve at least a two point improvement on the RI scale had atypical disease activity in only the larynx.

Twelve (80%) patients achieved a combined (secondary) endpoint of a decrease on the RI of two or more points at day 169, with no steroid use after day 57, and no disease flares.

All primary responders had sustained responses through the end of the trial.

The one (7%) patient who did not meet clinical response criteria had a RI score of two at baseline and a score of one before withdrawing from the trial after the Day 71 dose due to lack of efficacy (an IgG4-RD RI score reduction of less than two).

One (7%) patient who did not meet clinical response criteria had a RI score of two at baseline and a score of one before withdrawing from the trial after the Day 71 dose due to lack of efficacy (an IgG4-RD RI score reduction of less than two).

Two responders also did not complete the trial:

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Thirteen (87%) patients experienced adverse events with the most common adverse event of GI infusion-related, including nausea, abdominal pain, and diarrhea.

Rapid and Sustained IgG4-RD RI Responses from Phase 2 Trial

Rapid and Sustained IgG4-RD RI Response from Phase 2 Trial

Furthermore, as shown in Figure 5 below, circulating B cell counts decreased by approximately 60% throughout the treatment period.

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Circulating plasmablasts also decreased quickly, by approximately 70 to 80%, and began returning following cessation of obexelimab.

Obexelimab inhibited B cell receptor-linked signaling pathways but did not induce B cell depletion.

Both reductions in circulating B cells without evidence of depletion during obexelimab treatment and their rapid rebound after treatment discontinuation suggest that obexelimab might lead to B cell sequestration (margination) in lymphoid organs or the bone marrow.

After the first dose of obexelimab, CD19 receptor occupancy was nearly 100% for most patients and remained at or near complete occupancy until after the last dose of obexelimab at day 155.

We believe these results are promising and support the continued development of obexelimab for the treatment of IgG4-RD and potentially other B cell-mediated I&I conditions.

Rapid Recovery of Systemic B Cells Upon Discontinuation

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None of these events were considered by the investigator to be related to obexelimab.

Certain patients also experienced mild to moderate IV infusion-related GI symptoms.

Certain patients also experienced mild to moderate and transient IV infusion-related GI symptoms.

The most common TEAEs were abdominal pain and nausea (4/20, 20.0%), vomiting (3/20, 15.0%), and diarrhea, chills, headache, nasal congestion and upper respiratory tract infection (2/20, 10.0%).

INDIGO Trial—Our Ongoing Global Phase 3 Trial in IgG4-RD

In November 2024, we completed enrollment of patients in our INDIGO Trial, a global Phase 3 registration-directed, double-blind, placebo-controlled trial to evaluate the safety and efficacy of SC obexelimab in patients with active IgG4-RD in a randomized controlled period followed by an optional open-label extension period.

Approximately 190 patients were enrolled in the RCP and all patients from the RCP will be eligible for the OLE period.

The trial is being conducted at approximately 100 sites in 20 countries.

The RCP consists of a screening period (Day -28 to Day -1) and a 52-week treatment period, during which 250 mg of obexelimab or placebo will be administered as an SC injection every seven days.

Following the 52-week RCP, eligible patients will have the opportunity to continue in an OLE period where all patients will receive obexelimab.

INDIGO Trial Schema

All patients were required to receive three to six weeks of GC treatment at a dose of 20 to 60 mg/day prednisone equivalent prior to randomization.

The required GC therapy could either have been newly initiated or an increase in long-term GC therapy (i.e., patient was previously on a dose of ≤ 10 mg/day prednisone equivalent).

The exact dose and taper schedule during the screening period and prior to randomization are at the discretion of the investigator.

However, on the day of randomization, patients must have had no disease activity and been at a dose of 20 mg/day prednisone equivalent.

Patients were randomized 1:1 to receive obexelimab or placebo.

The primary efficacy assessment was time to first IgG4-RD flare, as determined by the investigator and the AC.

If the investigator suspected an IgG4-RD flare, based on reappearance of previous signs/symptoms or appearance of new signs/symptoms of IgG4-RD, organ-specific diagnostic assessments were conducted, including a physical examination, imaging and/or testing of biochemical parameters specific to the involved organ(s), to correlate symptoms and to document disease activity.

The investigator then determined if an IgG4-RD flare occurred and whether the initiation of rescue therapy was required.

The AC independently reviewed these diagnostic assessments to determine if, in their judgement, the signs/symptoms represent a flare.

Rescue therapy outside of permitted GC therapy would result in discontinuation from obexelimab or placebo treatment, as the case may be.

The trial was designed with approximately 90% power to detect a hazard ratio of 0.376 using a one-sided log-rank test at a significance level equal to 0.025.

Secondary endpoints include:

52-week flare rate, the proportion of patients achieving complete remission, use and quantity of rescue medication and the change in GC-associated toxicity as measured by the Glucocorticoid Toxicity Index (“GTI”).

Patients who complete the RCP Week 52 visit and meet all OLE eligibility criteria will have the option to participate in the trial for up to an additional 116 weeks (104-week treatment period followed by a 12-week follow-up) in the OLE period.

During the OLE, all patients will receive obexelimab once every seven days beginning on Day 1 of the OLE period, regardless of their treatment assignment during the RCP.

The primary objectives for the OLE are to evaluate the safety and efficacy of obexelimab in patients with IgG4-RD.

Obexelimab for the Treatment of MS

We believe obexelimab’s differentiated mechanism of action as an inhibitor of B cell lineage supports its potential for the treatment of MS.

We believe obexelimab’s differentiated mechanism of action as an inhibitor of the B cell lineage supports its potential for the treatment of MS.

The role of B cells in the pathogenesis of MS has been demonstrated through the successful clinical development, approval and clinical use of anti-CD20 B cell targeting therapies of other companies, including OCREVUS (ocrelizumab) and KESIMPTA (ofatumumab), which selectively deplete peripheral CD20-expressing B cells.

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We believe this activity observed from B cells may contribute to both MS relapses as well as the underlying disease progression.

In the third quarter of 2024, we initiated the MoonStone Trial, a Phase 2, multicenter, randomized, double-blind, placebo-controlled trial, to evaluate the efficacy and safety of obexelimab in patients with RMS.

In October 2025, we announced positive results from the MoonStone trial of obexelimab in patients with RMS.

Obexelimab met the primary endpoint, demonstrating a statistically significant 95% relative reduction in the cumulative number of GdE T1 hyperintense lesions, which are markers of active inflammation, over week 8 and week 12 compared with placebo (p=0.0009).

The adjusted mean number of new GdE T1 hyperintense lesions per scan in the obexelimab group (n=72) was 0.01 (95% CI:

0.00, 0.06) compared to 0.23 (95% CI:

0.11, 0.51) with placebo (n=38).

Additionally, over weeks 8 and 12 of treatment, obexelimab significantly reduced the cumulative number of new and/or enlarging T2 weighted hyperintense lesions compared to placebo, which represent the amount of disease burden or chronic lesion load.

The safety profile of obexelimab was consistent with that observed in prior completed trials, including cases of infections and hypersensitivity, most commonly mild injection site reactions.

In February 2026, we reported the 24-week data from the MoonStone trial which further confirmed the robust and durable activity of obexelimab.

The highly statistically significant reductions in total GdE T1 hyperintense lesions observed with obexelimab over weeks 8 and 12, when compared to placebo, were maintained when evaluating the obexelimab arm patients through week 24;

unadjusted mean number of new lesions per scan were 0.87 at baseline, 0.08 at week 12 and 0.04 at week 24 for obexelimab indicating a 95% reduction.

Additionally, obexelimab meaningfully reduced serum Neurofilament Light (“NfL”) by 40% through week 24;

15.28 pg/mL at baseline declining to 12.7 pg/mL at week 12 and 9.2 pg/mL at week 24.

New and/or enlarging T2 lesions were also lower in the obexelimab arm and the Expanded Disability Status Scale (“EDSS”) scores were stable, indicating a lack of progression in physical disability.

No new safety signals were observed at week 24.

As we continue to evaluate the MoonStone data and consider next steps for clinical development in this indication, we will consider, among other items, the evolving treatment landscape in RMS, including existing therapies, current pivotal trial endpoints and prioritization of capital.

MS Histology and Disease Background

MS is the most common immune-mediated, chronic inflammatory demyelinating disease of the central nervous system (“CNS”), affecting over two million people worldwide including as many as 1,000,000 in the U.S., according to the National MS Society and the MS Foundation.

MS is the most common immune-mediated, chronic inflammatory demyelinating disease of the CNS, affecting over two million people worldwide including as many as 1,000,000 in the U.S., according to the National MS Society and the MS Foundation.

We estimate a diagnosed prevalence of approximately 650,000 patients in the U.S.

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Patients with RRMS experience episodes of neurological dysfunction followed by complete or incomplete recovery.

Over time, the majority of RRMS patients develop disease progression, with or without relapses, referred to as secondary progressive MS (“SPMS”).

Over time, the majority of RRMS patients develop disease progression, with or without relapses, referred to as SPMS.

Patients with RRMS and SPMS with relapses are typically referred to as having RMS.

Lastly, 10 to 15% of patients present with a gradually progressive disease course from onset known as primary progressive MS (“PPMS”).

Lastly, 10 to 15% of patients present with a gradually progressive disease course from onset known as PPMS.

Most patients initially diagnosed with RRMS experience two distinct clinical phases, the relapsing-remitting and progressive phases, each of which is reflected by a distinct pathological process.

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Currently, the cause of MS remains unknown;

however, both B and T cells play an important role in the pathogenesis of the disease, including inflammation and demyelination process.

however, both B and T cells play an important role in the pathogenesis of the disease, including inflammation and demyelination processes.

In addition to producing autoantibodies and inflammatory cytokines, B cells have an important function as antigen-presenting cells (“APCs”) involved in T cell activation.

The APC function of B cells is thought to be an important reason for the beneficial effects of B cell therapies in MS.

The APC function of B cells is thought to be an important reason for the beneficial effects of anti-B cell therapies in MS.

Chronic CNS inflammation in the MS lesion is maintained, in part, with activated pro-inflammatory macrophages, microglia and astrocytes at the rim of chronic active or slowly expanding MS lesions, which are the site of ongoing demyelination and neuronal damage.

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Role of B and T Cells in Multiple Sclerosis

The potential efficacy of obexelimab in the treatment of MS has been demonstrated preclinically in a prophylactic disease animal model.

An obexelimab surrogate antibody (XENP8206) was evaluated versus a rituximab surrogate antibody and vehicle control in a preclinical experimental autoimmune encephalomyelitis (“EAE”) model.

As shown in Figure 7 below, XENP8206 prevented disease incidence to a greater extent than the rituximab surrogate antibody and the activity of XENP8206 was not associated with B cell depletion.

Suppression of Disease Activity in EAE Model Without B Cell Depletion

Current Treatment, Limitations and Remaining Unmet Need

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Monitoring the change in these MRI contrast enhancing lesions is routine and decreased MRI activity represents the earliest treatment effects in clinical trials.

In many MS Phase 3 trials, including those of B cell therapies, reductions in inflammatory lesions, initially demonstrated in Phase

2 POC trials utilizing MRI endpoints, were often accompanied by clinical improvements.

In many MS Phase 3 trials, including those of B cell therapies, reductions in inflammatory lesions, initially demonstrated in Phase 2 POC trials utilizing MRI endpoints, were often accompanied by clinical improvements.

The paramagnetic rim lesion may serve as another important emerging MRI marker of chronic neuroinflammation, with any modification observed in a clinical trial potentially indicating a change in disease progression.

In the third quarter of 2024, we initiated a Phase 2 potential POC trial of obexelimab in RMS patients, utilizing various MRI detection techniques and biomarkers to assess its impact in both the acute and chronic aspects of the disease.

To date, there are a number of therapies that have been approved for the treatment of MS, including injectable, oral and infused medications.

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Our Global Phase 2 Trial in RMS

Given the clinical activity observed with B cell depleting agents, we are currently enrolling patients in the MoonStone Trial, a global Phase 2 potential POC trial of obexelimab in RMS patients.

We expect to enroll approximately 93 patients and to conduct the trial at multiple sites worldwide.

The Phase 2 trial in RMS is a randomized, placebo-controlled trial in patients with relapsing active forms of MS in order to assess the safety and efficacy of a 250 mg weekly SC dose of obexelimab, utilizing various MRI detection techniques and biomarkers to assess its impact in both the active and chronic aspects of the disease.

The primary objective of this trial is to assess the change from baseline in the cumulative number of new Gd-enhancing lesions identified on T1-weighted MRI over the course of three months.

Upon completion of the three-month period, patients on placebo will receive obexelimab treatment for at least three months and patients initially randomized to obexelimab will continue on treatment.

Important secondary endpoints include changes in various other MRI assessments (i.e., changes in T2-weighted lesions, changes in the number of new phase RIM lesions, number of T1 lesion conversions to phase RIM lesions, etc.).

We expect to report data from the MoonStone Trial on the primary endpoint at 12 weeks in the third quarter of 2025.

The Phase 2 MoonStone trial, which enrolled 116 patients, is a randomized, double-blind, placebo-controlled trial, to evaluate the efficacy and safety of obexelimab in patients with RMS.

The trial follows a standard design using magnetic resonance imaging (MRI) endpoints.

After an initial screening period, patients were randomized 2:1 to receive either 250 mg of obexelimab or placebo via subcutaneous injection once weekly over a 12-week double-blinded treatment period.

The primary endpoint is the cumulative number of new Gd-enhancing T1 hyperintense lesions over week 8 and week 12

as measured by brain MRI.

Secondary and exploratory endpoints include using standardized assessments, imaging, and biomarkers to evaluate the impact on disease progression.

Upon completion of the double-blinded phase, all patients entered a 12-week open-label period in which those previously on placebo transition to obexelimab treatment, while those originally assigned to obexelimab continue therapy.

During the open-label period, secondary and exploratory endpoints will assess obexelimab’s clinical activity through week 24.

Obexelimab for the Treatment of SLE

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These responsive immunophenotype

subgroups are thus consistent with the drug’s mechanism of action, inhibition of B cell, plasmablasts, and plasma cell activity, an impact that was observed in patients treated with obexelimab.

subgroups are thus consistent with the drug’s mechanism of action, inhibition of B cell, plasmablast, and plasma cell activity, an impact that was observed in patients treated with obexelimab.

We believe the obexelimab efficacy data in the overall trial population and the increased response in biomarker-defined subpopulations, coupled with the safety data obtained to date, provide support for further clinical trials and the use of a SC obexelimab formulation in patients with SLE.

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We expect to enroll approximately 190 patients and to conduct the trial at multiple sites worldwide.

We expect to complete enrollment of the SunStone Trial in 2025 and report data on the primary endpoint at 24 weeks in the first half of 2026.

We expect to report data on the primary endpoint at 24 weeks and biomarker data in the fourth quarter of 2026.

To be eligible for the trial, patients enrolled must have active SLE at screening, as defined by BILAG 2004 and hSLEDAI.

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Additional biomarker assessments include serum cytokines and chemokines, SLE disease markers (complement C3/ C4, anti-dsDNA), and immune cell subsets (B cells, plasma cells, etc.).

Obexelimab for the Treatment of wAIHA – SApHiAre Trial

In December 2024, we announced preliminary results from patients in the open-label SRP of the Phase 2 portion of our SApHiAre Trial, a global study of obexelimab in patients with wAIHA.

The primary objectives of the SRP are to provide preliminary safety, tolerability, PK/PD and efficacy data of obexelimab in patients with wAIHA.

Patients were given 250 mg obexelimab weekly through subcutaneous administration for 24 weeks.

The primary efficacy endpoint in the SRP is proportion of patients with a hemoglobin (“Hgb”) ≥ 10 g/dL and ≥ 2 g/dL increase from baseline on or after Week 8, with no use of blood transfusion or GC rescue therapy prior to attaining response.

As of the cut-off date, nine patients had been enrolled in the SRP over an approximately one-year period, including eight patients with primary wAIHA and one patient with secondary wAIHA due to autoimmune disease.

One patient had not reached week four by the cut-off date and was not included in the analysis.

Five of eight patients achieved an increase of >1 g/dL of Hgb from baseline during weeks 8-24 without influence of concomitant medications.

Additionally, a Hgb increase of ≥ 2 g/dL measured from Hgb nadir to peak was observed in five of eight patients.

LDH and total bilirubin levels decreased overall during weeks 8-24.

No patients received transfusions.

Obexelimab was well tolerated in patients with wAIHA with a safety profile similar to that observed in earlier studies.

While we believe that the preliminary results from the SApHiAre Trial established proof of mechanism through an increase in Hgb and a positive effect on other clinical markers, we have determined not to progress to a registration-directed trial of obexelimab for the wAIHA indication based on several factors, including the expected length and expense of potential Phase 3 trial.

Safety Profile of Obexelimab

In the completed studies, 198 subjects have received obexelimab, 158 subjects as an IV infusion at doses of up to 10 mg/kg and 40 subjects as a SC injection of up to 375 mg.

In the clinical studies, including INDIGO and MoonStone, 383 subjects have received obexelimab, 158 subjects as an IV infusion and 225 subjects as a SC injection.

The majority of TEAEs in the studies using obexelimab were mild or moderate.

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The clinically non-important identified risks of obexelimab, defined as non-serious and related events, included intravenous infusion related GI events and injection site reactions via the SC administration.

The injection

site reactions were of minimal clinical impact, non-serious, did not lead to study drug discontinuation, and are anticipated to occur in less than 2% of injections.

The injection site reactions were of minimal clinical impact, non-serious and did not lead to study drug discontinuation.

The IV infusion related GI events were non-serious and were not observed with SC injection.

Serious Adverse Events

The only SAEs considered by the investigator to be related to obexelimab or placebo across the five clinical studies completed to date were:

The only SAEs considered by the investigator to be related to obexelimab or placebo across the clinical studies completed to date were:

two IV infusion related reactions, one in each of two obexelimab treated patients, one venous thrombosis in an obexelimab treated patient, one herpes zoster in a placebo treated patient and a post herpetic neuralgia in a placebo treated patient.

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Eight subjects (8/36, 22.2%) who had received 0.2 to 10 mg/kg obexelimab had their IV infusion temporarily interrupted as a result of the GI-related symptoms.

In all cases, symptoms leading to infusion interruption were transient and subjects were able to continue the infusion after a short break without recurrence of symptoms.

In all cases, symptoms leading to infusion

interruption were transient and subjects were able to continue the infusion after a short break without recurrence of symptoms.

Symptom resolution did not require the use of concomitant medications.

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This patient recovered fully and discontinued the trial.

There was one case of pneumonia accounting for two SAEs (initial and recurrence due to non-compliance with therapy) in one patient and a second patient experienced one SAE (chronic inflammation demyelinating

polyradiculoneuropathy in the setting of small lymphocytic lymphoma (pre-existing)).

None of the SAEs were considered to be related to obexelimab.

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Dosage and Administration for Obexelimab

Obexelimab has been evaluated in eight clinical trials, including INDIGO and MoonStone, in which a total of 383 subjects have received obexelimab either as an IV infusion at doses of up to 10 mg/kg (n=158) or as a SC injection at doses up to 375 mg (n=225).

We believe these trials have demonstrated obexelimab’s PK/PD and tolerability profile.

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In vitro , co-engagement of CD19 and FcγRIIb by obexelimab results in the inhibition of calcium mobilization upon stimulation of B cells from normal volunteers as well as in RA and SLE patients.

In vivo , obexelimab demonstrated inhibition of an induced human B cell response to immunization with tetanus toxoid in severe combined immunodeficient mice engrafted with human peripheral blood mononuclear cells.

In addition, obexelimab demonstrated disease improvement in several animal models of disease, including collagen-induced arthritis, AIHA and MS.

Obexelimab has shown no antibody-dependent cellular cytotoxicity mediated B cell depletion in vitro, nor has there been any significant obexelimab-mediated IL-6 or TNF-α cytokine release.

Obexelimab has shown no antibody-dependent cellular cytotoxicity mediated B cell depletion of complement directed cytotoxicity in vitro.

We are also developing ZB014, an anti-CD-19 and FcγRIIb monoclonal antibody designed to extend half-life, which is currently being evaluated in pre-clinical studies.

Orelabrutinib (Bruton’s Tyrosine Kinase inhibitor) Program

Orelabrutinib, also known as ZB020, is a highly selective and CNS-penetrant, oral small molecule BTK inhibitor.

Orelabrutinib is designed to bind irreversibly to BTK with minimal off-target effects, compared to certain other BTK inhibitors, which may potentially reduce certain side effects.

BTK is a member of the TEC family and is expressed in B lymphocytes, mast cells, macrophages, monocytes, and neutrophils.

We believe orelabrutinib is designed to efficiently cross the blood-brain barrier, reaching therapeutic levels within the CNS to directly target inflammation in diseases like MS.

This CNS penetration may be important for addressing the underlying disease pathology of progressive forms of MS, which is characterized by compartmentalized neuroinflammation and neurodegeneration.

Clinical Pharmacology

I n a central nervous system lymphoma (“CNSL”) study, CSF was collected 2 hours post-dose at steady state from 7 patients receiving a dose of 150 mg QD.

The mean CSF concentration of orelabrutinib was 31.3 ng/mL.

Based on the linear PK of orelabrutinib, the extrapolated CSF concentration at 80 mg QD is 16.7 ng/mL.

Based on a cell-free enzymatic kinase assay, the in vitro IC50 was measured as 0.7 ng/mL and the IC90 calculated to be 3.5 ng/mL.

Collectively, these data project that the CNS concentration of orelabrutinib exceeds the IC90 by approximately 5 fold.

No significant food effects were observed when orelabrutinib was administered with a standard high-fat, high-calorie meal.

BTK occupancy was achieved at doses of ≥50 mg/day for 24 hours after dosing.

Orelabrutinib for the Treatment of MS

A significant unmet need exists in MS for CNS-penetrant mechanisms that address compartmentalized local inflammation and directly impact the biology of progressive disease and neurodegeneration.

BTK inhibition could potentially address the underlying biology of progressive disease by impacting peripherally and centrally located pathogenic B cells and macrophages, and directly inhibiting microglia in the CNS.

See the section titled “MS Histology and Disease Background” for more information.

Over time, the majority of RMS patients develop disease progression, with or without relapses, referred to as SPMS.

SPMS is an advanced manifestation of RMS where relapses become less frequent or stop but gradual worsening of disability occurs.

There are three subtypes of SPMS:

active SPMS, non-relapsing SPMS and non-active SPMS.

Non-active SPMS is a progressive disease with no new relapses or MRI activity.

Ten to 15% of patients present with a gradually progressive

disease course from onset known as PPMS, which characterized as a steady increase in disability without relapses or disease flares.

We estimate a diagnosed prevalence of approximately 90,000 patients with non-active SPMS and approximately 60,000 to 100,000 patients with PPMS in the U.S.

SPMS and PPMS have the highest unmet need across MS subtypes, with limited therapeutic options.

Currently no treatments are approved for non-relapsing/non-active SPMS and there is only one approved treatment, Ocrevus, for PPMS.

We estimate that the commercial opportunity for MS could exceed $30 billion, over $12 billion attributable to non-active SPMS and PPMS combined.

Phase 2 Study of Orelabrutinib in RMS

In late 2024, the results of the Phase 2 trial of orelabrutinib for the treatment of RMS were announced.

The Phase 2 trial was a global, double-blind, placebo-controlled trial.

The primary endpoint was the cumulative number of new gadolinium-enhancing (“Gd+”) T1 brain lesions at Week 12 (based on new Gd+ T1 lesions at Weeks 4, 8, and 12) compared to placebo.

The results of the Phase 2 trial demonstrated that treatment with orelabrutinib resulted in a rapid and deep reduction in new Gd+ T1 lesions across all evaluated doses.

In the trial, 158 eligible RMS patients were randomized in a 1:1:1:1 ratio to one of four treatment groups:

placebo, orelabrutinib 50 mg once daily (“QD”), orelabrutinib 80 mg QD, and orelabrutinib 50 mg twice daily (“BID”).

Subjects in the placebo group were switched to orelabrutinib 50 mg QD at Week 13.

Phase 2 Study of Orelabrutinib in RMS Schema

At Week 12, all three treatment groups showed statistically significant reductions in the cumulative number of new Gd+ T1 lesions and new/enlarging T2 lesions compared to the placebo group (p < 0.05).

At week 24, the 80 mg QD and 50 mg BID groups showed statistically significant reductions compared to the placebo/50 mg QD group (p < 0.05).

The 80 mg QD group demonstrated the highest reductions in new Gd+ T1 lesions of 90.4% at Week 12 compared to placebo and 92.3% at Week 24 compared to the placebo/50 mg QD group.

New lesion control in each orelabrutinib group occurred at the earliest assessment timepoint of Week 4 and was sustained through Week 24.

Safety Summary

Orelabrutinib was generally well tolerated in the Phase 2 study of patients with RMS.

The known potential risks of orelabrutinib, as observed in clinical trials in patients with B-cell malignancies and autoimmune disease, include those associated with BTK inhibitor treatment such as hepatotoxicity, hemorrhage, cytopenia, infection, malignancy, hypertension, and arrhythmia.

In the Phase 2 RMS trial, 151 patients received at least one dose of orelabrutinib.

TEAEs leading to drug discontinuation occurred in 2.6% of patients.

The majority of TEAEs were Grades 1 or 2.

Observed Grade 3 or higher events primarily included hematologic toxicities and infections, which are mechanism-related and commonly reported with BTK inhibitor treatment.

Elevation of liver enzyme levels classified as hepatotoxicity were observed in the Phase 2 RMS trial (ICP-CL-00112), as well as in Phase 1/2 trials in patients with SLE (ICP-CL-00109 and ICP-CL-00124) and Phase 2/3 trials in patients with Immune Thrombocytopenia (ICP-CL-00116 and ICP-CL-00126).

Two cases of elevated liver enzymes and bilirubin met Hy’s Law criteria, one in the Phase 2 RMS trial and the other in the SLE trial.

Both affected patients were asymptomatic and their liver markers normalized after treatment was discontinued.

FDA issued a partial clinical hold for the conduct of the ongoing RMS trial.

Three other BTK inhibitors, including those currently in development for progressive MS, were also placed on a partial clinical hold while under development in the U.S.

No development restrictions were placed by the EMA.

In the Phase 3 progressive MS trials, for which no partial clinical hold is imposed, weekly liver function monitoring will be conducted during the first 12 weeks of treatment, which will be implemented through an established hepatotoxicity management scheme.

In addition, the safety of the study, including hepatotoxicity, will be monitored by an Independent Data Monitoring Committee (“IDMC”) and a Hepatoxicity Assessment Committee (“HAC”) through periodic or ad hoc reviews of study safety observations.

Orelabrutinib has been approved for commercial use for chronic lymphocytic leukemia and small lymphocytic lymphoma in China since December 2020.

PriMroSe Trial – Our Global Phase 3 Trial in Primary Progressive Multiple Sclerosis (PPMS)

In September 2024, InnoCare and the FDA reached an agreement to initiate a Phase 3 trial of orelabrutinib in patients with PPMS.

The FDA also encouraged InnoCare to initiate a second Phase 3 clinical trial of orelabrutinib in Progressive Multiple Sclerosis (“PMS”) within the SPMS population.

In February 2025, InnoCare reached alignment with the FDA on the Phase 3 clinical trial protocol for SPMS.

In September 2025, the Phase 3, PriMroSe Trial of orelabrutinib in patients with PPMS was initiated.

The PriMroSe Trial is a global, multicenter, randomized, double-blind, placebo-controlled clinical trial evaluating the safety and efficacy of orelabrutinib dosed 80 mg once daily QD compared to placebo in patients with PPMS, with a primary endpoint of time to onset of 12-week composite confirmed disability progression (“cCDP”), with a goal to report topline results in 2030.

We expect to enroll approximately 705 patients and to conduct the trial at over 300 sites worldwide.

PriMroSe Trial Schema

Monarch Trial – Our Global Phase 3 Trial in non-active Secondary Progressive Multiple Sclerosis

In the first quarter of 2026, we plan to initiate a second global, Phase 3, multicenter, randomized, double-blind, placebo-controlled clinical trial evaluating orelabrutinib dosed 80 mg QD compared to placebo in patients with non-active SPMS, with a primary endpoint of time to onset of 24-week CDP, and with a goal to report topline results in 2030.

We expect to enroll approximately 990 patients and to conduct the trial at over 300 sites worldwide.

Monarch Trial Schema

Early-Development Product Candidates:

ZB021 and ZB022

We also in-licensed from InnoCare certain exclusive rights to two early-development product candidates:

ZB021, an oral IL-17AA/AF inhibitor designed to block both IL-17AA homodimer and IL-17AF heterodimer signaling, and ZB022, an oral, brain-penetrant TYK2-JH2 inhibitor.

ZB021, is an oral IL-17AA/AF inhibitor.

As demonstrated in Figure 12 below, IL-17 is a pro-inflammatory cytokine secreted by immune cells in response to IL-23-dependent and -independent signals.

Normally Il-17 predominately acts at mucosal and epithelial surfaces to provide defense against bacterial and fungal infections.

Il-17 is implicated in multiple immune-mediated diseases by driving chronic inflammation in dermatological and rheumatological indications leading to manifestation such as skin thickening and joint inflammation.

Substantial clinical efficacy and the approval of several biologics targeting Il-17 or its receptor (Cosentyx®, Taltz®, Siliq®, and Bimzelx®), establishes IL-17 as a well-validated target for immune-mediated diseases.

Preclinical studies for ZB021 have shown favorable PK and ADME properties.

ZB021 achieved comparable activity in vivo to a reference anti-IL-17 biologic in a rat CIA model, as demonstrated in Figure 13 below.

We expect Phase 1 clinical study initiation in 2026, with the potential for initial clinical data in patients in 2027.

ZB021 Activity in Rat CIA Model

We believe ZB021 provides an opportunity for Zenas to expand its pipeline within rheumatology and into other therapeutic areas including dermatology.

Anti-IL-17 biologics are a drug class focused on the treatment of rheumatic and dermatologic diseases that we estimate currently represents an approximately $10 billion commercial opportunity, with an average of approximately 50% annual growth since the first approval of a product was obtained.

ZB022 is an oral, brain-penetrant TYK2-JH2 inhibitor currently in IND-enabling studies.

Subject to the results of IND-enabling studies, Zenas expects to submit an IND application for ZB022, and if cleared, initiate a Phase 1 clinical study in 2026, with the potential for initial clinical data in 2027.

TYK2 is an enzyme expressed inside immune cells and a member of the JAK-STAT family of kinases critical for cytokine signaling.

Normally TYK2-mediated signaling orchestrates adaptive and innate immune responses, including responses by helper T cell subsets and myeloid cells, involved in host defense against infectious agents.

In inflammatory conditions, dysregulated signaling through TYK2 drives pathological processes downstream of type 1 interferons and the IL-12/IL-23 cytokine axis.

TYK2 inhibition allows for a more targeted approach to cytokine inhibition, with approval of the first Tyk2 inhibitor (Sotyktu), establishing TYK2 as a viable target for immune-mediated diseases.

More recently, TYK2 has been implicated in driving neuroinflammation by resident immune cells and neuronal cells in multiple sclerosis and neurodegenerative diseases, indicating that a brain-penetrant TYK2 inhibitor has the potential to modulate pathogenic processes in the central nervous system, as demonstrated in Figure 14 below.

Other Programs

Beyond our lead product candidate, obexelimab, we have two other programs for the potential treatment of other I&I indications that we may continue to advance and ultimately commercialize with partners.

We have two other programs for the potential treatment of other I&I indications that we may continue to advance and ultimately commercialize with partners.

These consist of ZB002 (an anti-TNFα monoclonal antibody) and ZB004 (a CTLA-4-Ig fusion).

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In the second quarter of 2024, we initiated a Phase 1b MAD study of ZB002 in patients with rheumatoid arthritis.

A head-to-head preclinical study in mice demonstrated ZB002’s extended (≥ 2-fold longer) half-life over adalimumab.

Anti-TNFα Background and Mechanism of Action

TNFα is a potent inflammatory cytokine, produced primarily by activated monocytes, macrophages and T cells, as a cell surface protein.

After being activated, TNFα is released and binds to receptors on TNFα-responsive cells to enhance the inflammation and immune response to environmental stimuli such as foreign antigens.

Elevated expression of TNFα has been linked to a number of I&I diseases, and inhibition of TNFα signaling has been validated as a therapeutic approach to treat several diseases.

The FDA and other comparable foreign regulatory agencies have approved five anti-TNFα therapies to treat diseases, including rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, psoriasis, ulcerative colitis, hidradenitis suppurativa, and uveitis.

Among those approved therapies are Remicade (infliximab), Simponi (golimumab) and Humira (adalimumab), monoclonal antibodies that target TNFα for inhibition.

Summary of Clinical Trials

We conducted a Phase 1 SAD study designed to evaluate the safety, tolerability, PK and PD profiles of ZB002 in healthy volunteers.

We enrolled 48 healthy volunteers across six cohorts of varying dose levels, ranging from 20 mg to 240 mg, for the study.

Eight healthy volunteers were randomized 3:1 to ZB002 or placebo, per cohort.

There was one SAE of peri-anal abscess.

Our Phase 1 SAD study demonstrated a half-life of approximately 55 days for ZB002, which we believe may allow for dosing once every four to eight weeks.

In the second quarter of 2024, we initiated a Phase 1b MAD study of ZB002 in patients with rheumatoid arthritis.

If the results of our ongoing Phase 1b MAD study of ZB002 are favorable, we may seek to identify a partner to advance ZB002 in subsequent trials and ultimately, if approved, commercialize ZB002 for potential use as a treatment for certain I&I diseases that can benefit from TNFα inhibition.

Preclinical Characterization

ZB002 has similar pharmacological characteristics to adalimumab, including TNFα binding and inhibition.

The EC50 for in vitro inhibition of TNFα signaling is roughly equivalent (18.17 ng/mL for ZB002 and 14.25 ng/mL for adalimumab), and ZB002 and adalimumab inhibited TNFα-induced lethality in in vivo mouse models at similar rates.

However, ZB002 has a higher fragment crystallizable receptor (“FcRn”) binding affinity (KD = 6.54 ×10 −8 M) compared to adalimumab (KD = 1.88 ×10 −6 M), which is designed to extend ZB002’s in vivo half-life.

In the human neonatal FcRn expressed transgenic mice, the PK profile of ZB002 was found to be similar to that of adalimumab with the exception of an extended (≥ 2-fold longer) half-life (t1/2 = 9.9 hours and 4.1 hours for ZB002 and adalimumab, respectively).

The subcutaneous bioavailability of ZB002 was 62.4% to 106.0% in cynomolgus monkeys, depending on the dose.

Weekly subcutaneous administration of ZB002 for 13 weeks in cynomolgus monkeys demonstrated no adverse safety findings at any dose tested up to 200 mg/kg, providing an adequate therapeutic window for assessment in humans.

ZB004 Program (CTLA-4-IG fusion)

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Based on the results from our ongoing Phase 1 study, we plan to evaluate the path forward for the development of ZB004 in the treatment of I&I indications.

CTLA-4-Ig Background and Mechanism of Action

ZB004 is comprised of two CTLA-4 extracellular domain substitutions and an IgG Fc region containing substitutions (Xencor’s Xtend technology).

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Its mechanism of action is selective inhibition of T cell co-stimulation by binding to CD80 and CD86 receptors, which blocks their interaction with CD28 on T cells.

In rheumatoid arthritis, T cells contribute to lymphoid organogenesis in the inflamed joint and neoangiogenesis, stimulate synoviocyte proliferation, and support the development of osteoclasts.

CTLA-4, a protein expressed on the surface of CD4+ and CD8+ T cells, is an inhibitory receptor with high homology to the costimulatory receptor CD28.

It acts as a negative regulator of CD28-mediated activation of CD4+ and CD8+ T cells.

CTLA-4-Ig fusion proteins disrupt binding of CD28 with ligand B7 molecules, CD80 and CD86, expressed on antigen-presenting cells.

Inhibition of this signaling pathway results in a suppression of T cell effector function and is clinically validated by the regulatory approval of two CTLA-4-Ig therapeutics in several I&I diseases:

Orencia (abatacept) and Nulojix (belatacept).

Clinical Development

We conducted a Phase 1 SAD study designed to evaluate the safety, tolerability, PK immunogenicity and PD profiles of ZB004 in healthy volunteers.

Our Phase 1 SAD study enrolled 40 healthy volunteers across five cohorts of varying dose levels, ranging from 3 mg to 200 mg, with eight healthy volunteers randomized 3:1 to ZB004 or placebo, per cohort.

Our Phase 1 SAD study demonstrated a half-life of approximately 17.4 days at the highest dose level of 200 mg, where CD86 receptor occupancy reached a maximum peak value of 81%, overcoming the effect of target mediated drug disposition.

There were no SAEs reported.

Preclinical Characterization

ZB004 has been engineered to increase its affinity to human CD80 and CD86 by approximately six-fold compared to abatacept.

ZB004 also binds with higher affinity to human FcRn which is expected to extend ZB004 half-life in vivo .

ZB004 has shown potency by inhibiting T cell activity and cytokine release.

In an in vitro functional inhibition assay of T cell activity, the mean half-maximal inhibitory concentration (“IC50”) value was 0.334 µg/mL for ZB004 (2 donors) and > 50 µg/mL for abatacept.

When the inhibition of inflammation cytokine release was assessed, the IC50 values for interleukin 2 (IL-2) secretion driven by ZB004 or abatacept were < 0.003 µg/mL and 0.152 µg/mL, respectively.

The IC50 values for interferon gamma secretion driven by ZB004 and abatacept were 0.0054 µg/mL and > 50 µg/mL, respectively.

ZB004 has shown prophylactic efficacy in a collagen-induced arthritis disease model.

ZB004 was well tolerated in toxicology studies up to 13 weeks via subcutaneous administration in cynomolgus monkeys and rats, providing an adequate therapeutic window for assessment in humans.

In addition, ZB004 has a PK profile in animals with a dose-disproportional increase in exposure.

The terminal half-life parameter of ZB004 was determined at least 1.39-fold longer than that of abatacept in cynomolgus monkeys.

The subcutaneous bioavailability of ZB004 was 45.4% to 72.5% for rats and 73.4% to 79.9% for cynomolgus monkeys, depending upon the doses.

Partnered Regional Programs

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This mechanism of action has been clinically and commercially validated by the only FDA product approved for the treatment of thyroid eye disease (“TED”), Tepezza (teprotumumab).

TED is a debilitating condition that significantly impacts quality of life

and can cause proptosis, double vision and vision loss.

In October 2020, we entered into an exclusive license with Viridian, to develop, manufacture, and commercialize certain IGF-1R directed antibody products, including ZB001, for non-oncology indications in greater China.

Pursuant to our agreement with Viridian, we are obligated to reimburse Viridian for certain CMC and development expenses, and pay Viridian upon achievement of development milestones and royalties on net sales.

With our sublicense to Zai, Zai will pay for the reimbursement obligations and provide us with specified milestones and royalties.

For more information on our agreement with Viridian, see the section titled “Certain Relationships and Related Party Transactions—Director Affiliations—Agreements with Viridian Therapeutics Inc.”

In April 2023, we completed a Phase 1 SAD study in China in healthy volunteers showing ZB001 was well tolerated when administered in doses up to 20 mg/kg.

In April 2024, we completed the last patient visit in the Phase 1 MAD study of ZB001 in Chinese patients with active TED.

Preliminary data showed significant and rapid improvement in both signs and symptoms after 4 infusions of ZB001 in both 2 dose cohorts of 3mg/kg and 10mg/kg.

All AEs were mild or moderate in severity and no SAEs were reported.

On January 24, 2025, we entered into the Zai License Agreement with Zai, under which we granted Zai an exclusive sublicense to develop and commercialize ZB001 and related programs in greater China.

In January 2025, we entered into the Zai License Agreement with Zai, under which we granted Zai an exclusive sublicense to develop and commercialize ZB001 and related programs in greater China.

As partial consideration for the Zai License Agreement, we received an upfront fee of $10.0 million from Zai.

In addition, on October 21, 2024, we entered into the Tenacia Agreement, under which we transferred to Tenacia our rights and obligations under our agreements with Dianthus for ZB005.

In addition, in October 2024, we entered into the Tenacia Agreement, under which we transferred to Tenacia our rights and obligations under our agreements with Dianthus for ZB005.

As partial consideration for the Tenacia Agreement, we received an upfront fee of $5.0 million from Tenacia.

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We subsequently relinquished rights to the third product candidate back to Xencor and that asset is no longer a 2020 Licensed Asset.

Xencor obtained the rights to some of the intellectual property licensed to us pursuant to license agreements between Xencor and a third party (each such agreement, an “Upstream License Agreement”).

As such, the 2020 Xencor Agreement provides that the parties agree that some of the licenses granted by Xencor to us constitute sublicenses under the Upstream License Agreements and are subject, and subordinate, to the terms and conditions of the Upstream License Agreements.

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On a region-by region basis and product-by-product basis, the term during which the royalties are payable by us to Xencor is until the latest of (a) last-to-expire licensed patent covering the product in the applicable region, (b) the expiration of regulatory exclusivity for the product in the applicable region, or (c) the twelfth anniversary of the first commercial sale of the product in the applicable region.

The last-to-expire patent under the 2020 Xencor Agreement will have an expiration

date of December 22, 2028 for ZB002 and February 22, 2031 for ZB004, provided the latest application in each of these countries is allowed.

The expected termination of the royalty obligations will depend on factors such as the filing of additional patents covering the products during the term of the 2020 Xencor Agreement, the availability and application of patent term extensions and/or expiration of regulatory exclusivity for the products in the applicable region.

The last-to-expire patent under the 2020 Xencor Agreement will have an expiration date of December 22, 2028 for ZB002 and February 22, 2031 for ZB004, provided the latest application in each of these countries is allowed.

of patent term extensions and/or expiration of regulatory exclusivity for the products in the applicable region.

We are obligated to reimburse Xencor for certain third-party costs as further specified under the 2020 Xencor Agreement.

During the years ended December 31, 2024 and 2023, no costs and immaterial third-party costs were reimbursed, respectively.

During the years ended December 31, 2025 and 2024, no costs were reimbursed, respectively.

Under the 2020 Xencor Agreement, (i) Xencor owns all know-how and patent rights invented solely by Xencor, (ii) we own all know-how and patent rights invented solely by us;

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We are further required to use commercially reasonable efforts to commercialize obexelimab following regulatory approvals in certain specified countries (U.S., UK, France, Germany, Italy, and Spain).

We were obligated to

make development milestone payments of up to $10.0 million, at Xencor’s option either in cash or fully-paid newly issued shares, which milestone payment was paid in Series B Preferred Shares in June 2023.

We were obligated to make development milestone payments of up to $10.0 million, at Xencor’s option either in cash or fully-paid newly issued shares, which milestone payment was paid in Series B Preferred Shares in June 2023.

We are obligated to make regulatory milestone payments up to $75.0 million.

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License Agreement with Bristol-Myers Squibb

On August 30, 2023 (the “BMS Effective Date”), we entered into a strategic license and collaboration agreement with BMS (the “BMS Agreement”) under which we provided (a) an exclusive (even as to us) license under certain of our patents and joint patents to be developed under the BMS Agreement, and (b) a non-exclusive license under certain of our know-how.

The license grants are for BMS to (a) develop, manufacture (subject to our rights to be the exclusive manufacturer for BMS for a certain period of time), commercialize or otherwise exploit our proprietary CD19 x FcγRIIb antibody, obexelimab (the “Compound”) and any biological product (irrespective of presentations, formulations or dosages) containing the Compound but not any of our other proprietary active ingredient (the “Product”) for treatment of any disease in human or animal in the BMS Territory and (b) conduct development and manufacture of the Compound and Products outside the BMS Territory provided that the Compound and Product are solely used in the BMS Territory.

We also provided BMS a non-exclusive and royalty-free license under the same patent and know-how rights for BMS to develop,

manufacture, commercialize, or otherwise exploit companion diagnostics for the Compound and Products in the BMS Territory.

In August 2023 (the “BMS Effective Date”), we entered into a strategic license and collaboration agreement (the “BMS Agreement”) with Bristol-Myers Squibb (“BMS”) under which we provided (a) an exclusive (even as to us) license under certain of our patents and joint patents to be developed under the BMS Agreement, and (b) a non-exclusive license under certain of our know-how.

The license grants are for BMS to (a) develop, manufacture (subject to our rights to be the exclusive manufacturer for BMS for a certain period of time), commercialize or otherwise exploit our proprietary CD19 and FcγRIIb antibody, obexelimab (the “Compound”) and any biological product (irrespective of presentations, formulations or dosages) containing the Compound but not any of our other proprietary active ingredient (the “Product”) for treatment of any disease in human or animal in Japan, South Korea, Taiwan, Singapore, Hong Kong and Australia (the “BMS Territory”) and (b) conduct development and manufacture of the Compound and Products outside the BMS Territory provided that the Compound and Product are solely used in the BMS Territory.

We also provided BMS a non-exclusive and royalty-free license under the same patent and know-how rights for BMS to develop, manufacture, commercialize, or otherwise exploit companion diagnostics for the Compound and Products in the BMS Territory.

We retain all rights to commercialize obexelimab outside of the BMS Territory.

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On a country-by-country basis, the term during which the royalties are payable to us is until the latest of (a) the last-to-expire licensed patent covering the Product, (b) the expiration of regulatory exclusivity for the Product or (c) the twelfth anniversary of the first commercial sale of the Product.

As of the date of this prospectus, the last-to-expire patent under the BMS Agreement will have an expiration date of October 2, 2044, provided the latest application in each of these countries is allowed.

As of the date of this Annual Report, the last-to-expire patent under the BMS Agreement will have an expiration date of October 2, 2044, provided the latest application in each of these countries is allowed.

The expected termination of the royalty obligations will depend on factors such as the filing of additional patents covering the Product during the term of the BMS Agreement, the availability and application of patent term extensions and/or expiration of regulatory exclusivity for the Product in the BMS Territory.

Finally, BMS will be required to pay a portion of the costs associated with our ongoing INDIGO Trial, in which BMS is participating, as well as any other global study in which BMS elects to participate.

During the years ended December 31, 2024 and 2023, we recorded $6.0 million and $4.1 million, respectively, as a reduction to research and development expense for costs associated with our INDIGO Trial that will be reimbursed by BMS.

We recognized no revenue during the fiscal year ended December 31, 2024 pursuant to the BMS Agreement.

During the years ended December 31, 2025 and 2024, we recorded $5.5 million and $6.0 million, respectively, as a reduction to research and development expense for costs associated with our INDIGO Trial, including the OLE, that have been reimbursed by BMS.

During the fiscal years ended December 31, 2025 and 2024, we did not recognize revenue pursuant to the BMS Agreement.

The BMS Agreement will remain in effect, on a country-by-country basis, until the expiration of all royalty payment obligations, and may be earlier terminated by either party for the other party’s uncured material breach or insolvency.

BMS may terminate for convenience on a country-by-country basis with advance notice to us, with the notice period differing based on whether such termination right is exercised prior to or following the first commercial sale.

In addition to customary events of termination, we also have a right to terminate the agreement (a) automatically upon written notice if the upstream Xencor License Agreement terminates and (b) with written notice if BMS challenges the licensed patents.

In addition to customary events of termination, we also have a right to terminate the agreement (a) automatically upon written notice if the 2020 Xencor Agreement terminates and (b) with written notice if BMS challenges the licensed patents.

Upon termination of the BMS Agreement, all licenses granted by us to BMS will automatically terminate and BMS is obligated to cease developing, manufacturing (subject to any transition assistance) and commercializing the Compound and Products in the BMS Territory.

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BMS is obligated to provide reasonable transition supply assistance with respect to any agreement for manufacturing Compound or Products transferred to us, including manufacturing the Compound or Products for up to 18 months following termination.

License Agreement with InnoCare Pharma Inc.

In October 2025, we entered into a License Agreement (the “InnoCare License Agreement”) with InnoCare to obtain exclusive rights to develop, manufacture, and commercialize:

i) orelabrutinib, in the MS field worldwide, and in all non-oncology indications outside greater China and Brunei, Burma, Cambodia, Timor-Leste, Indonesia, Laos, Malaysia, Philippines, Singapore, Thailand and Vietnam (“Southeast Asia”), ii) ZB021 (an IL-17AA/AF inhibitor) in all fields of use worldwide, excluding greater China and Southeast Asia and iii) ZB022 (a TYK2 inhibitor) in all fields of use worldwide.

We also obtained certain non-exclusive rights to perform development and manufacturing activities in greater China and Southeast Asia to support each program in its respective licensed territories.

Pursuant to the InnoCare License Agreement, made a one-time non-refundable upfront cash payment of $35.0 million, which was recorded in the consolidated statement of operations and comprehensive loss as acquired in-process research and development expenses for the year ended December 31, 2025.

We issued 5,000,000 shares of common stock to InnoCare in a private placement as partial consideration for these rights.

We are also required to make an additional one-time non-refundable cash payment of $25.0 million and issue an additional 2,000,000 shares of common stock through a private placement upon the occurrence of our initiation of a Phase 3 clinical trial for orelabrutinib in any indication other than PPMS, or by March 31, 2026, upon the occurrence of certain specified events, whichever comes first (together with the 5,000,000 shares issued to InnoCare upfront, the “InnoCare Shares”).

During the year ended December 31, 2025, we recorded $136.7 million of expense based on fair value of the 5,000,000 shares issued and the 2,000,000 shares to be issued to InnoCare on the date the InnoCare License Agreement was executed, in the consolidated statement of operations and comprehensive loss as acquired in-process research and development expense.

In addition, we have agreed to make one-time, potential near-term milestone payments of $20.0 million each, upon the achievement of certain regulatory milestones for ZB021 and ZB022 (the “Regulatory Milestones”).

We are further obligated to pay future regulatory and commercial milestones of up to $723.0 million related to orelabrutinib, and future development, regulatory, and commercial milestones of up to $656.0 million, inclusive of the two $20.0 million Regulatory Milestones specified above, for each preclinical compound if certain milestones are successfully achieved.

In addition, we may be obligated to pay royalties on net sales at rates ranging from high-single digits to high-teens for orelabrutinib, and mid-single digits to mid-teens for the preclinical compounds.

We simultaneously entered into a Subscription Agreement and a Registration Rights Agreement with InnoCare related to the shares of common stock issued and to be issued in the private placements.

The Subscription Agreement provides for transfer restrictions on the InnoCare Shares and contains other customary representations, warranties and covenants that were made solely for the benefit of the parties to the Subscription Agreement.

The Registration Rights Agreement requires us to among other things, prepare and file a registration statement to register the InnoCare Shares.

Intellectual Property

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Patent Portfolio

As of March 11, 2025, we own or exclusively in-license 14 patent families that specifically cover our product candidates obexelimab (our CD19 x FcγRIIb antibody), ZB002 (our anti-TNFα antibody), and ZB004 (our CTLA-4-Ig fusion protein).

As of February 1, 2026, we own or exclusively in-license 28 patent families that specifically cover our product candidates obexelimab (our CD19 and FcγRIIb antibody), orelabrutinib (our BTK inhibitor), ZB002 (our anti-TNFα antibody), ZB004 (our CTLA-4-Ig fusion protein), ZB021 (our IL-17AA/AF inhibitor) and ZB022 (our TKY2 inhibitor).

These families include 25 issued U.S.

patents, nine pending U.S.

applications, 123 issued foreign patents, four pending PCT applications and 41 pending foreign patent applications in Australia, Brazil, Canada, China, Eurasia, Europe, Hong Kong, Israel, Japan, Malaysia, Mexico, New Zealand, Saudi Arabia, Singapore, South Africa, South Korea, Taiwan and the United Arab Emirates.

In addition, we own or exclusively in-license eight U.S.

provisional patent applications, which belong to four different patent families, within the priority year.

patents, 13 pending U.S.

applications, 198 issued foreign patents, seven pending patent cooperation treaty (“PCT”) applications and 88 pending foreign patent applications in Australia, Brazil, Canada, China, Colombia, Eurasia, Europe, Hong Kong, India, Israel, Japan, Malaysia, Mexico, New Zealand, Saudi Arabia, Singapore, South Africa, South Korea, Taiwan and the United Arab Emirates.

In addition, we own or exclusively in-license seven U.S.

provisional patent applications, which belong to five different patent families, within the priority year.

or foreign patents issued from national stage filings of our owned, or exclusively in-licensed PCT patent applications, any U.S.

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patents or foreign patents issued from non-provisional applications we may file in connection with our provisional patent applications would be scheduled to expire on various dates from 2027 through 2047.

All expected expiration dates provided herein are based on a 20-year term, without taking into account any possible PTA or PTE and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees.

All expected expiration dates provided herein are based on a 20-year term, without taking into account any possible patent term adjustment (“PTA”) or patent term extension (“PTE”) and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees.

Obexelimab is a bifunctional, non-cytolytic, humanized monoclonal antibody that binds CD19 and FcγRIIb to inhibit B-lineage cell activity.

As of March 11, 2025, we own or exclusively in-license from Xencor ten patent families that specifically cover the composition of matter, mechanism of action, manufacturing, biomarkers and the clinical uses of obexelimab for treating IgG4-RD, SLE, MS and wAIHA.

A first patent family specifically covers the composition of matter of obexelimab and includes six issued patents and two pending applications in the U.S., and 21 issued foreign patents in Australia, Hong Kong, India, Israel and various European countries including Belgium, Denmark, France, Germany, Ireland, Italy, Latvia, Lithuania, Luxembourg, Monaco, Netherlands, Spain, Sweden, Switzerland, and UK.

As of February 1, 2026, we own or exclusively in-license from Xencor 14 patent families that specifically cover the composition of matter, mechanism of action, formulation, manufacturing, biomarkers, and clinical uses of obexelimab for treating IgG4-RD, SLE, MS and wAIHA.

A first patent family specifically covers the composition of matter of obexelimab and includes seven issued patents and one pending applications in the U.S., and 21 issued foreign patents in Australia, Hong Kong, India, Israel and various European countries including Belgium, Denmark, France, Germany, Ireland, Italy, Latvia, Lithuania, Luxembourg, Monaco, Netherlands, Spain, Sweden, Switzerland, and UK.

The 20-year statutory term for the patents issued in this family expires in May 2028, excluding any extension of patent term that may be available.

A second patent family is directed to obexelimab’s mechanism of action and includes one issued patent and one pending application in the U.S., five pending applications in Canada, Europe, Hong Kong and Japan, and 20 issued patents in Japan and European countries including Austria, Belgium, Denmark, France, Finland, Germany, Hungary, Ireland, Italy, Netherlands, Norway, Poland, Portugal, Spain, Switzerland, Sweden, Turkey and UK.

A second patent family is directed to obexelimab’s mechanism of action and formulation, which includes two issued patents and one pending application in the U.S., five pending applications in Canada, Europe, Hong Kong and Japan, and 20 issued patents in Japan and European countries including Austria, Belgium, Denmark, France, Finland, Germany, Hungary, Ireland, Italy, Netherlands, Norway, Poland, Portugal, Spain, Switzerland, Sweden, Turkey and UK.

The 20-year statutory term for any patents issued in this family expires in June 2037, excluding any extension of patent term that may be available.

A third patent family is directed to the use of biomarkers for treating autoimmune diseases (e.g., SLE) and includes one pending U.S.

application, and 13 pending applications in Australia, Brazil, Canada, China, Eurasia, Europe, Hong Kong, Israel, Japan, South Korea, Mexico, South Africa and Taiwan.

application, and 12 pending applications in Australia, Brazil, Canada, China, Europe, Hong Kong, Israel, Japan, South Korea, Mexico, South Africa and Taiwan and one issued patent in Eurasia.

The 20-year statutory term for any patents issued in this family would expire in October 2041, excluding any extension of patent term that may be available.

A fourth patent family is directed to the clinical use of obexelimab for treating IgG4-RD, currently including one pending U.S.

Application, and 17 pending applications in Australia, Brazil, Canada, China, Eurasia, Europe, Isreal, Japan, Malaysia, Mexico, New Zealand, Saudi Arabia, Singapore, South Africa, South Korea, Taiwan and the United Arab Emirates.

Application, and 20 pending applications in Australia, Brazil, Canada, China, Eurasia, Europe, Hong Kong, Israel, Japan, Malaysia, Mexico, New Zealand, Saudi Arabia, Singapore, South Africa, South Korea, Taiwan and the United Arab Emirates.

The 20-year statutory term for any patents issued in this family would expire in June 2043, excluding any extension of patent term that may be available.

A fifth patent family is directed to the clinical use of obexelimab for treating AIHA, including wAIHA, currently including a pending PCT application and a Taiwanese application.

A fifth patent family is directed to the clinical use of obexelimab for treating AIHA, including wAIHA, currently including one pending U.S.

application and six pending applications in Australia, Europe, Japan, South Korea, Singapore, and Taiwan.

The 20-year statutory term for any patents issued in this family would expire in April 2044, excluding any extension of patent term that may be available.

A sixth patent family is directed to the clinical use and dosing regimen of obexelimab for treating forms of MS, including RMS, and currently including a pending PCT application and a pending U.S.

A sixth patent family is directed to the clinical use and dosing regimen of obexelimab for treating forms of MS, including RMS, and currently including a pending PCT application, a pending U.S.

application, and a pending Taiwanese application.

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The 20-year statutory term for any patents issued in this family would expire in January 2045, excluding any extension of patent term that may be available.

A ninth patent family is directed to the manufacturing processes for obexelimab currently including one provisional application.

A ninth patent family is directed to the manufacturing processes for obexelimab currently including a pending PCT application, a pending U.S.

application, and a pending Taiwanese application.

The 20-year statutory term for any patents issued in this family would expire in June 2045, excluding any extension of patent term that may be available.

A tenth patent family is related to the clinical use of obexelimab for treating wAIHA and includes a pending PCT application, and a Taiwanese application.

The 20-year statutory term for any patents issued in this family would expire in October 2045, excluding any extension of patent term that may be available.

An eleventh patent family is directed to methods of determining potency of obexelimab currently including two provisional applications filed within the priority year.

Assuming the provisional application is converted to a non-provisional application at the 12-month from priority deadline, the 20-year statutory term for any patents issued in this family would expire in May 2046, excluding any extension of patent term that may be available.

A twelfth patent family is directed to methods of vaccination during treatment course with obexelimab currently including one provisional application filed within the priority year.

Assuming the provisional application is converted to a non-provisional application at the 12-month from priority deadline, the 20-year statutory term for any patents issued in this family would expire in June 2046, excluding any extension of patent term that may be available.

A tenth patent family is related to the clinical use of obexelimab for treating wAIHA currently including two provisional applications within the priority year.

Assuming the provisional applications are converted to a non-provisional application at the 12-month from priority deadline, the 20-year statutory term for any patents issued in this family would expire in October 2045, excluding any extension of patent term that may be available.

A thirteenth patent family is directed to the clinical use and dosing regimen of obexelimab for treating forms of MS, including RMS and SPMS, currently including two provisional applications filed within the priority year.

Assuming the provisional application is converted to a non-provisional application at the 12-month from priority deadline, the 20-year statutory term for any patents issued in this family would expire in October 2046, excluding any extension of patent term that may be available.

A fourteenth patent family is based on the Phase 3 clinical data of obexelimab for treating IgG4-RD currently including one provisional application filed within the priority year.

Assuming the provisional application is converted to a non-provisional application at the 12-month from priority deadline, the 20-year statutory term for any patents issued in this family would expire in January 2047, excluding any extension of patent term that may be available.

A PTE of up to five years may be available and can be applied in one of these families as appropriate.

Orelabrutinib

Orelabrutinib is a highly selective CNS-penetrant, oral small molecule BTK inhibitor.

As of February 1, 2026, we exclusively in-licensed seven patent families from InnoCare that specifically cover the composition of matter, polymorphs, amorphous solid dispersion form, synthetic processes, and the uses of orelabrutinib for treating multiple sclerosis and Alzheimer’s disease.

A first patent family covers the composition of matter of orelabrutinib and includes five issued patents and one pending patent application in the U.S., and 45 issued patents in Australia, Canada, India, Japan, South Korea, Mexico, New Zealand, Russia and various European countries including Albania, Austria, Belgium, Bulgaria, Croatia, Cyprus, Czechia, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Monaco, the Netherlands, North Macedonia, Norway, Poland, Portugal, Romania, San Marino, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey, and UK.

The 20-year statutory term for the patents issued in this family expires in September 2034, excluding any extension of patent term that may be available.

A second family covers the polymorphs of orelabrutinib and currently includes one issued patent in the U.S., four pending patent applications in Canada, India, Japan, and South Korea, and 10 issued patents in Australia, Mexico, New Zealand and various European countries including France, Germany, Italy, the Netherlands, Spain, Switzerland, and UK.

The 20-year statutory term for the patents issued in this family expires in September 2039, excluding any extensions of patent term that may be available.

A third family covers the amorphous solid dispersion form of orelabrutinib and currently includes one issued patent in the U.S., one pending patent application in Canada, and 13 issued patents in Australia, Japan, South Korea, Mexico, New Zealand and various European countries including Belgium, France, Germany, Italy, the Netherlands, Spain, Switzerland, and UK.

The 20-year statutory term for the patents issued in this family expires in October 2039, excluding any extensions of patent term that may be available.

A fourth family covers processes for synthesizing orelabrutinib and currently includes one issued patent in the U.S., four pending applications in Brazil, Canada, Europe, and South Korea, and six issued patents in Australia, India, Japan, Mexico,

New Zealand, and Russia.

The 20-year statutory term for the patents issued in this family expires in February 2040, excluding any extensions of patent term that may be available.

A fifth family covers improved processes for synthesizing orelabrutinib and currently includes one pending U.S.

application and 16 pending applications in Australia, Brazil, Canada, Colombia, Eurasia, Europe, Israel, India, Japan, Mexico, New Zealand, Saudi Arabia, South Africa, South Korea, and the United Arab Emirates.

The 20-year statutory term for any patents issued in this family would expire in July 2044, excluding any extensions of patent term that may be available.

A sixth family covers the use of orelabrutinib for treating multiple sclerosis and currently includes one pending U.S.

patent application and 10 pending patent applications in Australia, Canada, China, Europe, Hong Kong, Japan, South Korea, Mexico, New Zealand, and Singapore.

The 20-year statutory term for any patents issued in this family would expire in November 2043, excluding any extensions of patent term that may be available.

A seventh family covers the use of orelabrutinib for treating Alzheimer’s disease and currently includes a pending PCT application.

The 20-year statutory term for any patents issued in this family would expire in January 2045, excluding any extensions of patent term that may be available.

A PTE of up to five years may be available and can be applied in one of these families as appropriate.

ZB002 is an anti-TNFα monoclonal antibody with the Xtend technology modified to have an extended half-life as compared to existing anti- TNFα therapies.

As of March 11, 2025, we exclusively own or in-licensed two patent families covering ZB002.

As of February 1, 2026, we exclusively own or in-licensed three patent families covering ZB002.

A first patent family specifically covers the full-length amino acid sequences of ZB002, including four issued patents in the U.S., Brazil, Japan and Russia, and two pending applications in Europe and Hong Kong.

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The 20-year statutory term for any patents issued in this family would expire in March 2045.

A third patent family is directed to the manufacturing processes for ZB002 including one provisional application.

Assuming the provisional application is converted to a non-provisional application at the 12-month from priority deadline, the 20-year statutory term for any patents issued in this family would expire in September 2046, excluding any extension of patent term that may be available.

A PTE of up to five years may be available and can be applied in one of these families as appropriate.

ZB004 is a CTLA-4-Ig fusion protein with the Xtend technology modified to have an extended half-life versus existing CTLA-4-Ig fusion protein therapies.

As of March 11, 2025, we own or exclusively in-licensed two patent families relating to the composition of matter of ZB004 and related methods of use.

A first patent family specifically covers the composition of matter and related methods of use ZB004 including six issued patents and one pending application in the U.S., and 79 issued foreign patents in Australia, Canada, China, Hong Kong, India, Japan, South Korea and European countries including Albania, Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lichtenstein, Lithuania, Luxembourg, Macedonia, Malta, Monaco, Netherlands, Norway, Poland, Portugal, Romania, San Marino, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey, and UK.

As of February 1, 2026, we own or exclusively in-licensed two patent families relating to the composition of matter of ZB004 and related methods of use.

A first patent family specifically covers the composition of matter and related methods of use ZB004 including seven issued patents and 81 issued foreign patents in Australia, Canada, China, Hong Kong, India, Japan, South Korea and European countries including Albania, Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lichtenstein, Lithuania, Luxembourg, Macedonia, Malta, Monaco, Netherlands, Norway, Poland, Portugal, Romania, San Marino, Serbia, Slovakia, Slovenia,

Spain, Sweden, Switzerland, Turkey, and UK.

The 20-year statutory term for the patents issued in this family expires in February 2031, excluding any extension of patent term that may be available.

A second patent family is related to the formulation and dosing regimen of ZB004 in treating autoimmune diseases currently including two provisional applications within the priority year.

A second patent family is related to the formulation and dosing regimen of ZB004 in treating autoimmune diseases currently including one pending PCT application.

The 20-year statutory term for any patents issued in this family would expire in September 2045.

A PTE of up to five years may be available and can be applied in one of these families as appropriate.

ZB021 is a small molecule IL-17AA/AF inhibitor that blocks IL-17AA homodimer and IL-17AF heterodimer signaling for minimizing inflammatory responses.

As of February 1, 2026, we exclusively in-license from InnoCare one patent family that specifically covers the composition of matter.

This family includes one pending PCT application, and one pending U.S.

patent application.

The 20-year statutory term for the patents issued in this family expires in March 2045, excluding any extensions of patent term that may be available.

ZB022 is a small molecule brain-penetrant TYK2-JH2 inhibitor that blocks the TYK2-mediated receptor-stimulated pathways.

As of February 1, 2026, we exclusively in-license from InnoCare one patent family that specifically covers the composition of matter.

This family currently includes one pending PCT application.

The 20-year statutory term for the patents issued in this family expires in July 2045, excluding any extensions of patent term that may be available.

Trademark Portfolio

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and other foreign jurisdictions.

The Company also owns trademark applications and registrations related to potential drug name candidate trademarks in the U.S.

and other foreign jurisdictions.

Manufacturing

We do not own or operate, and currently have no plans to establish, any manufacturing facilities.

We have engaged, and currently rely on, a single third-party CMO, WuXi Biologics, for the supply of our product candidates for use in our preclinical studies and clinical trials.

In addition, we have selected new CMOs in the U.S., which are not affiliated with Wuxi Biologics, to establish additional sources of supply for drug substance and drug product for both commercial and clinical use.

However, should our CMO, Wuxi Biologics, become unavailable to us for any reason, we believe that we would incur delay and cost in order to complete the manufacturing validation and qualification process for such replacements.

We have engaged, and currently rely on, single source third-party CMO, WuXi Biologics, for the supply of obexelimab drug product, and our collaboration partner, InnoCare, for the supply of orelabrutinib, ZB021 and ZB022, for use in our preclinical and clinical trials.

In addition, we have selected new CMOs in the U.S., which are not affiliated with Wuxi Biologics, to establish additional sources of supply for obexelimab drug substance and drug product for both commercial and clinical use.

However, should our CMO, WuXi Biologics, or our collaboration partner, InnoCare, become unavailable to us for any reason, we believe that we would incur delay and cost in order to complete the manufacturing validation and qualification process for such replacements.

We maintain a master services agreement with Wuxi Biologics pursuant to which it provides biologics development and manufacturing services on a per-project basis.

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We have a long-term commercial supply agreement with WuXi Biologics to fulfill and secure obexelimab drug substance and drug product for an anticipated commercial launch, if approved.

In addition, we have selected new CMOs in the U.S., which are not affiliated with WuXi Biologics, to establish additional sources of supply for drug substance and drug product for both commercial and clinical use.

For the medical device component of our product (i.e., prefilled syringe or autoinjector), we plan to utilize device assembly facilities in the U.S.

In addition, we have selected new CMOs in the U.S., which are not affiliated with WuXi Biologics, to establish additional sources of supply for obexelimab drug substance and drug product for both commercial and clinical use.

For the medical device component of our product (i.e., prefilled syringe

or autoinjector), we plan to utilize device assembly facilities in the U.S.

or EU for the global supply.

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Sales, Marketing and Commercialization

None of our product candidates have been approved for sale in any country.

We hold global development and commercialization rights to obexelimab, excluding Japan, Taiwan, South Korea, Singapore, Hong Kong and Australia, which we have licensed to BMS.

We also hold the global development and commercialization rights to ZB002 and ZB004.

We also in-licensed from InnoCare certain exclusive rights to orelabrutinib and two early-development product candidates:

ZB021 and ZB022.

If our product candidates receive FDA or EMA approval, we intend to build our own commercialization infrastructure in the U.S.

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However, we intend to continually evaluate the economics of potentially commercializing our product candidates ourselves, if approved, versus other strategic commercialization arrangements.

We currently have no sales, marketing or commercialization capabilities and have no experience as a company performing such activities.

However, we intend to build the necessary capabilities and infrastructure over time as our product candidates continue to advance through clinical development.

We believe that clinical data, the size of the market

opportunity and the size of the required commercial infrastructure will influence our commercialization plans and decision making.

We currently have limited sales, marketing and commercialization capabilities as we are early in the process of building a commercial organization to support the potential launch of obexelimab in the U.S.

We intend to continue to build the necessary capabilities and infrastructure over time We believe that clinical data, the size of the market opportunity and the size of the required commercial infrastructure will influence our commercialization plans and decision making.

The biotechnology and pharmaceutical industries are characterized by rapidly advancing technologies, intense competition and a strong emphasis on proprietary drugs.

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We are currently developing obexelimab for IgG4-RD, MS, and SLE.

There are currently no approved products for IgG4-RD.

A number of products are approved for MS and two products are approved for SLE.

However, there are a number of product candidates in clinical development by other companies for IgG4-RD, MS, and SLE which may become available in the future.

In April 2025, FDA approved Uplizna® (inebilizumab-cdon), an anti-CD19 antibody, which is the first and only FDA-approved therapy for adults with IgG4-RD.

There are also two products approved for SLE, and a number of products approved for MS.

Moreover, there are a number of product candidates in clinical development by other companies for IgG4-RD, MS, and SLE that may become available in the future.

We are also currently developing orelabrutinib for PPMS and non-active SPMS.

For PPMS, there is currently one FDA-approved therapy, Ocrevus ® (ocrelizumab), a humanized anti-CD20 monoclonal antibody marketed by F.

Hoffmann-La Roche Ltd.

For non-active SPMS, there are currently no FDA-approved therapies.

Additional product candidates in clinical development by other companies may become available for PPMS and non-active SPMS in the future.

Potentially competitive therapies by indication fall primarily into the following groups of treatment:

● UPLIZNA (inebilizumab-cdon), an anti-CD19 antibody being developed by Amgen Inc., for which Amgen filed a BLA and was granted Priority Review based on the results of its Phase 3 trial;

● a small molecule Bruton’s tyrosine kinase (“BTK”) inhibitor in a Phase 2 trial, being developed by Sanofi S.A.;

● Uplizna® (inebilizumab-cdon), an anti-CD19 antibody marketed by Amgen Inc.;

● Rilzabrutinib, a small molecule BTK inhibitor, currently in a Phase 3 trial and being developed by Sanofi S.A.;

● ACE1831, an allogeneic γδ2 T-cell therapy targeting CD20-expressing B cells, currently in Phase ½ trial, and being developed by Acepodia Inc.;

● other clinical or preclinical small molecules, biologics (including cell-based therapies), or other therapeutic modalities that may be or are being developed for IgG4-RD;

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Hoffmann-La Roche Ltd., Kesimpta ® marketed by Novartis AG, Briumvi ® marketed by TG Therapeutics Inc., an anti-CD52 antibody Lemtrada ® marketed by Sanofi S.A., and an α4-integrin antibody Tysabri ® marketed by Biogen;

● approved non-antibody-based injectable therapies including interferon beta-1a therapies such as Avonex marketed by Biogen, Plegridy marketed by Biogen, Betaseron marketed by Bayer AG, Extavia marketed by

Novartis AG, Rebif marketed by Merck KGaA, and myelin basic protein-based therapies such as Copaxone marketed by Teva Neuroscience Inc.;

● approved non-antibody-based injectable therapies including interferon beta-1a therapies such as Avonex ® marketed by Biogen, Plegridy ® marketed by Biogen, Betaseron ® marketed by Bayer AG, Extavia ® marketed by Novartis AG, Rebif ® marketed by Merck KGaA, and myelin basic protein-based therapies such as Copaxone ® marketed by Teva Neuroscience Inc.;

● approved small molecule oral therapies including Aubagio ® marketed by Genzyme Corporation, Bafiertam ® marketed by Banner Life Sciences, Gilenya ® marketed by Novartis AG, Mavenclad ® marketed by Merck KGaA, Mayzent ® marketed by Novartis AG, Ponvory ® marketed by Janssen Pharmaceuticals, Inc., Tascenso ® ODT marketed by Cycle Pharmaceuticals Ltd., Tecfidera ® marketed by Biogen, Vumerity ® marketed by Biogen, and Zeposia ® marketed by Bristol Myers Squibb Company;

● three small molecule BTK inhibitor programs in Phase 3 development by Sanofi S.A., Novartis AG, and Hoffmann-La Roche Ltd.;

● a vidofludimus calcium program in Phase 3 development by Immunic Therapeutics Inc.;

● a small molecule selective tyrosine kinase inhibitor program in Phase 3 development by AB Science;

● an anti-CD40/CD40L antibody in a Phase 3 trial being developed by Sanofi S.A;

● several Phase 2 trial programs evaluating multiple targets / mechanisms of action including but not limited to CD19, BTK, M1R (muscarinic type 1 receptor), BLyS/APRIL, MOG (myelin oligodendrocyte glycoprotein), VLA-4 (very late antigen 4), Treg cells, undisclosed targets / mechanisms and allogenic, autologous, mesenchymal, and CAR-T cell therapies;

● other clinical or preclinical disease modifying small molecules, biologics, or other therapeutic modalities that may be or are being developed for MS;

● and, approved generic and biosimilar therapies.

● approved therapies including an anti-BLyS antibody Benlysta marketed by GSK plc., an anti-IFNAR (type I interferon receptor) antibody Saphnelo marketed by AstraZeneca plc., and a dual antagonist of BlyS and APRIL Tai’ai approved and marketed only in China, by RemeGen Co., Ltd.;

● an anti-CD40L (CD40 ligand) pegylated Fab (antigen binding fragment) program in a Phase 3 clinical trial, being developed by UCB Biopharma SRL;

● an anti-BDCA2 (blood dendritic cell antigen 2) antibody program in Phase 3 trials, being conducted by Biogen Inc.;

● a dual antagonist of BLyS and APRIL program in a Phase 3 (ex-China) trial, being developed by RemeGen Co., Ltd.;

● two anti-CD20 antibody programs in Phase 3 trials, being developed by F.

● two small molecule BTK inhibitor programs in Phase 3 development, including remibrutinib by Novartis AG, and fenebrutinib by Hoffmann-La Roche Ltd.;

● a vidofludimus calcium program, vidofludimus, in Phase 3 development by Immunic Therapeutics Inc.;

● an anti-CD40/CD40L antibody, frexalimab, in Phase 3 trial development by Sanofi S.A.;

● several Phase 2 trial programs evaluating multiple targets / mechanisms of action including but not limited to CD19, BTK, TYK2, BLyS/APRIL, PAD, Treg cells, stem cell therapy, CAR-T cell therapies and undisclosed targets / mechanisms;

● other clinical or preclinical disease modifying small molecules, biologics, or other therapeutic modalities that may be or are being developed for RMS;

● an approved generic and biosimilar therapies.

● Ocrevus ® (ocrelizumab), an anti-CD20 antibody marketed by F.

Hoffmann-La Roche Ltd.;

and Beijing Mabworks Biotech Co., Ltd., the latter in China only;

● a small molecule tyrosine kinase 2 (“TYK2”) inhibitor in Phase 3 trials, being developed by Bristol Myers Squibb Company;

● a sphingosine-1-phosphate 1 receptor modulator in Phase 3 trials, being developed by Idorsia Pharmaceuticals Ltd.;

● a small molecule Janus kinase inhibitor in Phase 3 trials, being developed by AbbVie Inc.;

● an anti-BAFF-R antibody program in Phase 3 trials, being developed by Novartis AG;

● several Phase 2 trial programs evaluating multiple targets / mechanisms of action including but not limited to TLR7/8, CD28/ICOS, CD40/CD40L, BAFF/APRIL, IL2, IL21, CRL4-CRBN, IFNB1, BTLA, FcRn, TYK2, BTK, CD22, CD32B/CD79B, CD19, a CD19 CAR-γδT program, CD19/CD20/BCMA-CAR T programs and undisclosed targets / mechanisms;

● a small molecule BTK inhibitor program, fenebrutinib, in Phase 3 development by F.

Hoffmann-La Roche Ltd.;

● a small molecule selective tyrosine kinase inhibitor program, masitinib, in Phase 3 development by AB Science;

● several Phase 2 trial programs evaluating multiple targets/mechanisms of action including but not limited to CD19, CD20, BTK, DHODH, Nurrl, MAGL, MHC class II modulators, Treg cells, CAR-T cell therapies and undisclosed targets/mechanisms;

● other clinical or preclinical disease modifying small molecules, biologics, or other therapeutic modalities that may be or are being developed for PPMS;

● an approved generic and biosimilar therapies.

● a small molecule BTK inhibitor program, tolebrutinib, that has completed Phase 3 study in non-relapsing SPMS and is being developed by Sanofi S.A.;

● a small molecule BTK inhibitor program, remibrutinib, in Phase 3 development in SPMS by Novartis AG;

● a small molecule selective tyrosine kinase inhibitor program, masitinib, in Phase 3 in development in non-active SPMS by AB Science;

● an anti-CD40/CD41 antibody, frexalimab, in Phase 3 development in non-relapsing SPMS by Sanofi S.A.;

● several Phase 2 trial programs evaluating multiple targets/mechanisms of action including but not limited to CD19, CD3, BTK, DHODH, Nurr1, stem cell therapy, CAR-T cell therapies and undisclosed targets/mechanisms;

● other clinical or preclinical disease modifying small molecules, biologics, or other therapeutic modalities that may be or are being developed for SPMS;

● approved generic and biosimilar therapies.

● approved therapies including an anti-BLyS antibody Benlysta ® (belimumab) marketed by GSK plc., an anti-IFNAR (type I interferon receptor) antibody Saphnelo ® (anifrolumab) marketed by AstraZeneca plc., and a dual antagonist of BlyS and APRIL Tai’ai ® (telitacicept) approved and marketed only in China, by RemeGen Co., Ltd.;

● an anti-CD40L (CD40 ligand) pegylated Fab (antigen binding fragment) program, dapirolizumab, in a Phase 3 clinical trial, being developed by UCB SA;

● an anti-BDCA2 (blood dendritic cell antigen 2) antibody program, litifilimab, in Phase 3 trials, being conducted by Biogen Inc.;

● a small molecule TYK2 inhibitor in Phase 3 trials, deucravacitinib, being developed by Bristol Myers Squibb Company;

● a sphingosine-1-phosphate 1 receptor modulator in Phase 3 trials, cenerimod, being developed by Idorsia Pharmaceuticals Ltd.;

● a small molecule Janus kinase inhibitor in Phase 3 trials, upadacitinib, being developed by AbbVie Inc.;

● an anti-BAFF-R antibody program in Phase 3 trials, ianalumab, being developed by Novartis AG;

● two anti-CD20 antibody programs in Phase 3 trials, including one program developed by F.

Hoffmann-La Roche Ltd.

that reported positive topline results in SLE, and a second program from Beijing Mabworks Biotech Co., Ltd., the latter in China only;

● several Phase 2 trial programs evaluating multiple targets / mechanisms of action including but not limited to BCL-2, BCMA/CD19, BCMA/CD3, BDCA-2, BlyS, BTK, CD19, CD19/CD3, CD20, CD20/CD3, CD22, CD38, cGAS, HK-4 glucokinase, IFNAR1, TLR7/8, TYK2, stem cell therapy, CAR-T cell therapies and undisclosed targets / mechanisms;

● other clinical or preclinical small molecules, biologics, or other therapeutic modalities that may be or are being developed for SLE;

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While these other therapies have not been shown to be effective, and carry significant side effects, their off-label use could reduce or delay treatment in the addressable patient population for obexelimab.

We are also developing ZB002, an anti-TNFα therapy with an extended half-life.

The TNFα-binding region within the fragment variable (Fv) domain has an identical amino acid sequence to Humira (adalimumab).

The fragment crystallizable (Fc) domain consists of a hybrid immunoglobulin (IgG1/2) constant region containing amino acid substitutions for extended half-life.

There are 5 FDA-approved innovator anti-TNF programs for various indications including Humira marketed by AbbVie Biotechnology Ltd., Enbrel marketed by Amgen Inc., Remicade, marketed by Janssen Biotech, Inc., Simponi, marketed by Janssen Biotech, Inc., and Cimzia, marketed by UCB, Inc.

In addition to these five innovator anti-TNF programs, a number of biosimilar anti-TNF programs are FDA-approved including Humira biosimilars (such as Amjevita marketed by Amgen Inc., Abrilada marketed by Pfizer Inc., Cyltezo marketed by Boehringer Ingelheim Pharmaceuticals, Inc., Hadlima Organon group of companies, Hulio marketed by Veritas Inc., Hyrimoz marketed by Sandoz Inc., Idacio marketed by Fresenius Kabi USA, LLC, Yuflyma marketed by Celltrion Healthcare Co., Ltd., and Yusimry marketed by Coherus BioSciences, Inc.).

ZB004 is a CTLA-4-Ig fusion protein with an extended half-life and potential improved potency versus existing CTLA-4-Ig fusion protein therapies.

There are two marketed CTLA-4-Ig fusion protein therapies.

Orencia, marketed by BMS, is FDA-approved for rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, and prophylaxis of acute graft versus host disease.

Nulojix, marketed by BMS, is FDA-approved for prophylaxis of organ rejection in adult patients receiving a kidney transplant.

One Orencia biosimilar program recently entered Phase 1 clinical development.

We are also developing ZB021, an oral IL-17 AA/AF inhibitor.

There are four FDA-approved IL-17 programs for various indications, all of which are in intravenous or subcutaneous formulations, including Cosentyx ® (secukinumab) marketed by Novartis AG, Taltz ® (ixekizumab) marketed by Eli Lilly and Company, Bimzelx ® (bimekizumab-bkzx) marketed by UCB SA, and Siliq ® (brodalumab) marketed by Bausch Health Companies Inc.

There are currently no FDA-approved IL-17 biosimilars.

There are several IL-17 programs in clinical development in the US, including oral small molecule and oral peptide programs such as simepdekinra by Eli Lilly and Company in Phase 2 development, PN-881 by Protagonist Therapeutics Inc.

in Phase 1 development, and ASC-50 by Ascletic Pharma Inc.

in Phase 1 development.

Additional oral IL-17 programs are in preclinical development.

We are also developing ZB022, a brain-penetrant TYK2 inhibitor.

There is one FDA-approved TYK2 inhibitor, Sotyktu ® (deucravacitinib) marketed by Bristol-Myers Squibb Company, indicated for adults with moderate-to-severe plaque psoriasis.

Sotyktu is a peripheral acting TYK2 inhibitor.

There are currently no FDA-approved TYK2 inhibitor biosimilars.

There are several TYK2 inhibitor programs in clinical development in the US, including the following Phase 3 programs:

zasocitinib, a peripheral acting TYK2 inhibitor being developed by Takeda Pharmaceutical Company Limited, envudeucitinib, a brain-penetrant TYK2 inhibitor being developed by Alumis Inc., and BHV-8000, a brain-penetrant TYK2/JAK1 inhibitor being developed by Biohaven Therapeutics Ltd.

Additional Phase 1 and Phase 2 clinical TYK2 programs, as well as preclinical TYK2 programs, are in development across numerous indications.

Government Regulation

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and in other countries and jurisdictions, including the EU, extensively regulate, among other things, the research, development, testing, manufacture, pricing, reimbursement, sales, quality control, approval, packaging, storage, recordkeeping, labeling, advertising, promotion, distribution, marketing, post-approval monitoring and reporting and import and export of biological products such as those we are developing.

We, along with our CMOs, CROs and third-party vendors, will be required to satisfy these requirements in each of the countries in which we wish to conduct studies or seek approval or licensure of our product candidates.

We, along with our CMOs, contract research organizations (“CROs”) and third-party vendors, will be required to satisfy these requirements in each of the countries in which we wish to conduct studies or seek approval or licensure of our product candidates.

The processes for obtaining marketing approvals in the U.S.

and in foreign countries and jurisdictions, along with subsequent compliance with applicable statutes, regulations, and other regulatory requirements, require the expenditure of substantial time and financial resources.

Licensure and Regulation of Biologics in the U.S.

We are currently developing product candidates that are biological products, or biologics.

In the U.S., where we are initially focusing our product development, the FDA regulates biologics under the FDCA and the Public Health Service Act (“PHSA”), and their implementing regulations.

Biologics are also subject to other federal, state and local statutes and regulations.

Our product candidates are early-stage and have not been approved for marketing in the U.S.

An applicant seeking approval to market and distribute a new biologic in the U.S.

In the U.S., where we are initially focusing our product development, the FDA regulates biologics and small molecule drugs under the Federal Food Drug and Cosmetic Act (“FDCA”) and Public Health Service Act (“PHSA”), and their implementing regulations.

Both biologics and small molecule drugs are also subject to other federal, state and local statutes and regulations.

Our product candidates have not been approved for marketing in the U.S.

An applicant seeking approval to market and distribute a new biologic or small molecule drug in the U.S.

must satisfactorily complete each of the following steps:

● preclinical laboratory tests, animal studies and formulation studies performed in accordance with the FDA’s GLPs;

● manufacture of the drug substance and drug product in accordance with the FDA’s cGMPs, along with required analytical and stability testing;

● submission to the FDA of an Investigational New Drug Application (“IND”) for human clinical testing, which must become effective before human clinical trials may begin;

● preclinical laboratory tests, animal studies and formulation studies performed in accordance with the FDA’s Good Laboratory Practices (“GLPs”);

● manufacture of the drug substance and drug product in accordance with the FDA’s current Good Manufacturing Practices (“cGMPs”), along with required analytical and stability testing;

● submission to the FDA of an IND for human clinical testing, which must become effective before human clinical trials may begin and must be updated annually or when significant changes are made;

● approval by an independent IRB, representing each clinical trial site before each clinical trial may be initiated;

● performance of adequate and well-controlled human clinical trials, in accordance with current Good Clinical Practice requirements (“cGCPs”), necessary to establish the safety, potency and purity of the product candidate for each proposed indication;

● preparation and submission to the FDA of a BLA, requesting marketing approval for one or more proposed indications, including submission of detailed information on the manufacture and composition of the product and proposed labeling;

● performance of adequate and well-controlled human clinical trials, in accordance with current Good Clinical Practice requirements (“cGCPs”), necessary to establish the safety, efficacy, potency and purity of the product candidate for each proposed indication;

● preparation and submission to the FDA of a New Drug Application (“NDA”) or BLA, requesting marketing approval for one or more proposed indications, including submission of detailed information on the manufacture and composition of the product and proposed labeling;

● a determination by the FDA within 60 days of its receipt of the BLA or NDA to file the application for review;

● satisfactory completion of one or more FDA inspections of the manufacturing facility or facilities, including those of third parties, at which the product, or components thereof, are produced to assess compliance with cGMPs and to assure that the facilities, methods and controls are adequate to preserve the product’s identity, strength, quality and purity;

● satisfactory completion of any FDA audits of the preclinical studies and clinical trial sites to assure compliance with GLPs and cGCPs, as applicable, and the integrity of clinical data in support of the BLA;

● payment of user fees under the Prescription Drug User Fee Act (“PDUFA”), unless exempted;

● the FDA’s review and approval of the BLA, including consideration of the views of any FDA advisory committee, if applicable;

● if approved, compliance with any post-approval requirements, including the potential requirement to implement a REMS and any post-approval studies or other post-marketing commitments required by the FDA.

● the FDA’s review and approval of the BLA or NDA, including consideration of the views of any FDA advisory committee, if applicable;

prior to any commercial marketing or sale of drug or biologic in the U.S.

● if approved, compliance with any post-approval requirements, including the potential requirement to implement a Risk Evaluation and Mitigation Strategy (“REMS”) and any post-approval studies or other post-marketing commitments required by the FDA.

Failure to comply with the applicable requirements at any time during the product development process, including preclinical testing, clinical testing, the approval process, or post-approval process, may subject an applicant to delays in the conduct of the study or regulatory review and approval, as well as administrative or judicial sanctions or other consequences.

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Preclinical tests include laboratory evaluations of product chemistry, formulation and stability, as well as studies to evaluate the potential for efficacy and toxicity in animals.

The conduct of preclinical tests and formulation of the compounds for testing must comply with federal regulations and

requirements, including GLPs.

The conduct of preclinical tests and formulation of the compounds for testing must comply with federal regulations and requirements, including GLPs.

The results of the preclinical tests, together with manufacturing information, analytical data, and plans for the proposed clinical studies, are submitted to the FDA as part of an IND.

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At any time during the initial 30-day IND review period or while clinical trials are ongoing under the IND, the FDA may impose a partial or complete clinical hold.

Clinical holds may be imposed by the FDA when there is concern for patient safety, and may be a result of new data, findings, or developments in clinical, preclinical, and/or chemistry, CMC or where there is non-compliance with regulatory requirements.

Clinical holds may be imposed by the FDA when there is concern for patient safety, and may be a result of new data, findings, or developments in clinical, preclinical, and/or chemistry, manufacturing and controls (“CMC”) or where there is non-compliance with regulatory requirements.

This order would delay either a proposed clinical trial or cause suspension of an ongoing trial, until all outstanding concerns have been adequately addressed and the FDA has notified the company that investigations may proceed.

A separate submission to an existing IND must also be made for each successive clinical trial conducted, and the FDA must grant permission, either explicitly or implicitly, by not objecting before each clinical trial can begin.

A separate submission to an existing IND must also be made for each successive clinical trial conducted, and the FDA must grant authorization, either explicitly or implicitly, by not objecting before each clinical trial can begin.

Human Clinical Trials

Clinical trials involve the administration of an investigational drug product to healthy volunteers or patients with the disease or condition to be treated under the supervision of qualified investigators.

Clinical trials must be conducted in accordance with GCPs, which establish ethical and data integrity standards for clinical testing, as well as the requirements for informed consent.

Clinical trials must be conducted in accordance with cGCPs, which establish ethical and data integrity standards for clinical testing, as well as the requirements for informed consent.

Clinical trials are conducted under protocols detailing, among other things, the objectives of the trial, dosing procedures, inclusion and exclusion criteria, the parameters to be used in monitoring safety, and the effectiveness criteria to be evaluated.

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An IRB must operate in compliance with FDA regulations.

The FDA, IRB or the trial sponsor may suspend a clinical trial at any time on various grounds, including a finding that the trial is not being conducted in accordance with GCPs or IRB requirements or that research subjects or patients are being exposed to an unacceptable health risk.

The FDA, Institutional Review Board (“IRB”) or the trial sponsor may suspend a clinical trial at any time on various grounds, including a finding that the trial is not being conducted in accordance with cGCPs or IRB requirements or that research subjects or patients are being exposed to an unacceptable health risk.

In addition, some clinical trials are overseen by an independent group of qualified experts organized by the sponsor, known as a data safety monitoring board or data monitoring committee.

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When a foreign clinical trial is conducted under an IND, all FDA IND requirements must be met unless waived.

When a foreign clinical trial is not conducted under an IND, FDA may accept the results of the study in support of a BLA if the study was well-designed and conducted in accordance with GCPs, and the FDA is able to validate the data through an onsite inspection if deemed necessary.

When a foreign clinical trial is not conducted under an IND, FDA may accept the results of the study in support of a BLA or NDA if the study was well-designed and conducted in accordance with cGCPs, and the FDA is able to validate the data through an onsite inspection if deemed necessary.

Clinical trials typically are conducted in three sequential phases, but the phases may overlap or be combined.

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● Phase 1 trials are initially conducted in a limited population of healthy subjects to test the product candidate for safety, including adverse effects, dose tolerance, absorption, metabolism, distribution, excretion and PD.

case of some products designed to address severe or life-threatening diseases, initial human testing is often conducted in patients with the disease, especially when the product may be too inherently toxic to ethically administer to healthy volunteers.

In the case of some products designed to address severe or life-threatening diseases, initial human testing is often conducted in patients with the disease, especially when the product may be too inherently toxic to ethically administer to healthy volunteers.

● Phase 2 trials are generally conducted in a limited patient population to identify possible adverse effects and safety risks, evaluate the preliminary efficacy of the product candidate for specific targeted indications and determine dose tolerance and recommended dosage.

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such Phase 3 studies are generally referred to as “pivotal,” however, for some investigational products, Phase 2 may be considered pivotal trials if such trials are expected to provide the clinical evidence needed to support a marketing application.

In some cases, the FDA may approve a BLA for a product but require the sponsor to conduct additional clinical trials to further assess the product’s safety and effectiveness after approval.

In some cases, the FDA may approve a BLA or NDA for a product but require the sponsor to conduct additional clinical trials to further assess the product’s safety and effectiveness after approval.

Such post-approval trials are typically referred to as confirmatory studies, or Phase 4 clinical trials.

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During the development of a new biologic, sponsors are given opportunities to meet with the FDA at certain points.

These points may be prior to submission of an IND, at the end of Phase 2, and before a BLA is submitted.

These points may be prior to submission of an IND, at the end of Phase 2, and before a BLA or NDA is submitted.

Meetings at other times may be requested.

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Additionally, appropriate packaging must be selected and tested and stability studies must be conducted to demonstrate that the products do not undergo unacceptable deterioration over their shelf life.

Before approving a BLA, the FDA will typically inspect the facility or facilities where the product is manufactured.

The FDA will not approve an application unless it determines that the manufacturing processes and facilities are in compliance with cGMPs and

adequate to assure consistent production of the product within required specifications.

Before approving a BLA or NDA, the FDA will typically inspect the facility or facilities where the product is manufactured.

The FDA will not approve an application unless it determines that the manufacturing processes and facilities are in compliance with cGMPs and adequate to assure consistent production of the product within required specifications.

The PHSA emphasizes the importance of manufacturing controls for products like biologics whose attributes cannot be precisely defined.

Material changes in manufacturing equipment, location, or process post-approval, may result in additional regulatory review and approval.

Review and Approval of a BLA

The results of clinical trials and preclinical studies, together with detailed information regarding the manufacturing processes, chemistry and composition of the product, the proposed labeling and other relevant information, are submitted to the FDA as part of a BLA requesting approval to market the product for one or more specified indications.

Clinical and preclinical data may come from company-sponsored trials or from a number of alternative sources, including studies initiated by investigators, and the BLA must include any negative and ambiguous results, as well as positive findings.

Review and Approval of a BLA/NDA

The results of clinical trials and preclinical studies, together with detailed information regarding the manufacturing processes, chemistry and composition of the product, the proposed labeling and other relevant information, are submitted to the FDA as part of a BLA or NDA requesting approval to market the product for one or more specified indications.

Clinical and preclinical data may come from company-sponsored trials or from a number of alternative sources, including studies initiated by investigators, and the BLA or NDA must include any negative and ambiguous results, as well as positive findings.

To support marketing approval, the data submitted must be sufficient in quality and quantity to establish the safety, purity, and potency of the investigational product to the satisfaction of the FDA.

For most BLAs, the sponsor is required to pay a substantial application user fee at the time of submission and the sponsor of an approved BLA is subject to an annual program fee.

For most BLAs or NDAs, the sponsor is required to pay a substantial application user fee at the time of submission and the sponsor of an approved BLA or NDA is subject to an annual program fee.

Certain exceptions and waivers are available for some of these fees, such as an exception from the application fee for products with orphan designation and a waiver for certain small businesses.

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Under the goals and policies agreed to by the FDA under PDUFA, the FDA has ten months from the acceptance date in which to complete its initial review of a standard application and respond to the applicant, and six months for a priority review of the application.

The FDA does not always meet its PDUFA goal dates for standard and priority BLAs and the review process may be significantly extended by FDA requests for additional information or clarification.

The FDA does not always meet its PDUFA goal dates for standard and priority BLAs or NDAs and the review process may be significantly extended by FDA requests for additional information or clarification.

For example, the review process and the PDUFA goal date may be extended by three months if the FDA requests or if the applicant otherwise provides additional data, analysis or information that FDA deems a major amendment.

During its review of a BLA, the FDA may refer applications for novel biological products or biological products that present difficult questions of safety or efficacy to an advisory committee.

During its review of a BLA/NDA, the FDA may refer applications for novel drug or biological products, or drug or biological products that present difficult questions of safety or efficacy to an advisory committee.

Typically, an advisory committee is a panel of independent experts, including clinicians and other scientific experts, that reviews, evaluates and provides a recommendation as to whether the application should be approved and under what conditions, if any.

The FDA is not bound by the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions.

On the basis of the FDA’s evaluation of the application and accompanying information, including the results of the inspection of the manufacturing facilities and any FDA audits of preclinical and clinical trial sites to assure compliance with GLPs or GCPs, the FDA may approve the BLA or issue a complete response letter.

is not bound by the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions.

Under the PHSA, the FDA may approve a BLA if it determines the product is safe, pure, and potent, and that the facility in which the product will be manufactured, processed, packaged or held meets standards designed to assure the product’s continued safety, purity and potency.

Similarly, under the FDCA, the FDA may approve an NDA if it determines the product is safe and effective and that the facility in which the product will be manufactured, processed, packaged or held meets standards designed to assure the product’s continued safety and efficacy.

If FDA determines the product meets these standards, it may issue an approval letter authorizing the commercial marketing of the product with specific prescribing information for specific indications.

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In addition, the FDA may require post-approval studies, including Phase 4 clinical trials, to further assess the product’s efficacy and/or safety after approval.

agency may also require testing and surveillance programs to monitor the product after commercialization, or impose other conditions, including distribution restrictions or other risk management mechanisms, including REMS, to help ensure that the benefits of the product outweigh the potential risks.

REMS can include medication guides, communication plans for healthcare professionals and elements to assure safe use (also known as ETASU).

The agency may also require testing and surveillance programs to monitor the product after commercialization, or impose other conditions, including distribution restrictions or other risk management mechanisms, including REMS, to help ensure that the benefits of the product outweigh the potential risks.

REMS can include medication guides, communication plans for healthcare professionals and elements to assure safe use (“ETASU”).

ETASU can include, but are not limited to, special training or certification for prescribing or dispensing, dispensing only under certain circumstances, special monitoring and the use of patent registries.

The FDA may prevent or limit further marketing of a product based on the results of post-market studies or surveillance programs.

After approval, if there are any modifications to the approved product, including changes in the indications, dosage forms, labeling, or manufacturing processes or facilities, the sponsor may be required to submit and obtain FDA approval of a new BLA or BLA supplement, which may require the generation of additional data or the conduct of additional preclinical studies and clinical trials.

After approval, if there are any modifications to the approved product, including changes in the indications, dosage forms, labeling, or manufacturing processes or facilities, the sponsor may be required to submit and obtain FDA approval of a new BLA/NDA or BLA/NDA supplement, which may require the generation of additional data or the conduct of additional preclinical studies and clinical trials.

Post-Approval Regulation

Upon FDA approval of a BLA, the sponsor will be required to comply with all post-approval regulatory requirements for biologics, as well as any specific post-approval requirements that the FDA has imposed as part of the product or indication’s approval process.

Upon FDA approval of a BLA or NDA, the sponsor will be required to comply with all post-approval regulatory requirements for biologics, as well as any specific post-approval requirements that the FDA has imposed as part of the product or indication’s approval process.

The sponsor will be required to report certain adverse reactions and production problems to the FDA, provide updated safety and efficacy information, obtain FDA approval for certain manufacturing and labeling changes, and comply with requirements concerning advertising and promotional labeling, record-keeping, and drug supply chain security.

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If the product is subject to official lot release, the manufacturer must submit samples of each lot, together with a release protocol showing a summary of the history of manufacture of the lot and the results of all of the manufacturer’s tests performed on the lot, to the FDA.

The FDA may perform certain confirmatory tests on lots of some products before releasing the lots for distribution.

perform certain confirmatory tests on lots of some products before releasing the lots for distribution.

In addition, the FDA strictly regulates the marketing, labeling, advertising and promotion of prescription drug products, including biological products.

These regulations include, among other things, standards and regulations for direct-to-consumer advertising, communications regarding unapproved uses, industry-sponsored scientific and educational activities and promotional activities involving the internet and social media.

Promotional claims about a drug’s safety or effectiveness are prohibited before the BLA is approved.

Once a BLA is approved, the sponsor can make only those claims relating to safety, efficacy, purity and potency that are in accordance with the provisions of the approved label.

Promotional claims about a drug’s safety or effectiveness are prohibited before the BLA/NDA is approved.

Once a BLA/NDA is approved, the sponsor can make only those claims relating to safety, efficacy, purity and potency that are in accordance with the provisions of the approved label.

In the U.S., healthcare professionals are generally permitted to prescribe legally available drugs for uses that are not described in the product’s labeling and that differ from those approved by the FDA.

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These products are known as combination products.

We expect that obexelimab and our other product candidates packaged in a prefilled syringe or autoinjector would be subject to regulation as a combination product if consisting of a therapeutic biologic and a delivery device.

The constituent elements of such combination products would normally be subject to different FDA regulatory frameworks and regulated by different Centers at the FDA.

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Even when a single marketing application is required for a combination product, such as a BLA for a combination biologic and device product, both FDA’s Center for Biologics Evaluation and Research and FDA’s Center for Devices and Radiological Health may participate in the review.

If a product candidate is considered a biologic-device combination product, the sponsor will also need to comply with post-marketing regulatory requirements, including adverse event reporting and applicable portions of the FDA’s Quality System regulation, applicable to combination products.

If a product candidate is considered a combination product, the sponsor will also need to comply with post-marketing regulatory requirements, including adverse event reporting and applicable portions of the FDA’s Quality Management System regulation, applicable to combination products.

Fast Track, Breakthrough Therapy and Priority Review Designations

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These designations are not mutually exclusive, and a product candidate may qualify for one or more of these programs.

these programs are intended to expedite product development and approval, they do not alter the standards for FDA approval.

While these programs are intended to expedite product development and approval, they do not alter the standards for FDA approval.

The FDA may designate a product for fast track designation if it is intended for the treatment of a serious or life-threatening disease or condition, and preclinical or clinical data demonstrate the potential to address unmet medical needs for such a disease or condition.

For products with fast track designation, sponsors may have more frequent interactions with the FDA, the product is potentially eligible for accelerated approval and priority review, if relevant criteria are met, and the BLA may be eligible for “rolling review,” under which the FDA may consider sections of the BLA for review on a rolling basis before the complete application is submitted.

For products with fast track designation, sponsors may have more frequent interactions with the FDA, the product is potentially eligible for accelerated approval and priority review, if relevant criteria are met, and the BLA/NDA may be eligible for “rolling review,” under which the FDA may consider sections of the BLA for review on a rolling basis before the complete application is submitted.

This rolling review may be available if the FDA determines, after preliminary evaluation of clinical data submitted by the sponsor, that a product with fast track designation may be effective.

The sponsor must also provide, and the FDA must approve, a schedule for the submission of the remaining sections of the BLA, and the sponsor must pay any required user fees upon submission of the first section of the BLA.

The sponsor must also provide, and the FDA must approve, a schedule for the submission of the remaining sections of the BLA/NDA, and the sponsor must pay any required user fees upon submission of the first section of the BLA/NDA.

The FDA’s time goal for reviewing a fast track application does not begin until the last section of the application is submitted.

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The FDA may designate a product for priority review if it is a product that treats a serious condition and, if approved, would provide a significant improvement in safety or effectiveness when compared with other available therapies.

A priority review designation is intended to direct the FDA’s attention and resources to the evaluation of such applications, and to shorten the FDA’s goal for taking action on an original BLA from ten months to six months from the acceptance date.

A priority review designation is intended to direct the FDA’s attention and resources to the evaluation of such applications, and to shorten the FDA’s goal for taking action on an original BLA/NDA from ten months to six months from the acceptance date.

Fast track designation, breakthrough therapy designation, and priority review do not change the standards for approval but may expedite the development or approval process.

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The FDA’s approval of a candidate product under the accelerated approval pathway is usually contingent on a sponsor’s agreement to conduct post-approval confirmatory studies to verify and describe the product’s clinical benefit, and the FDA may require such studies to be underway prior to approval.

Failure to conduct required post-approval studies, confirm a clinical benefit during post-marketing studies may result in the FDA’s withdrawal of the product from the market on an

expedited basis.

Failure to conduct required post-approval studies, confirm a clinical benefit during post-marketing studies may result in the FDA’s withdrawal of the product from the market on an expedited basis.

All promotional materials for therapeutic candidates approved under accelerated regulations are subject to prior review by the FDA.

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Orphan drug exclusivity means that the FDA may not approve another sponsor’s marketing application for the same product for the same indication for seven years, except in certain limited circumstances.

If a product designated as an orphan drug ultimately receives marketing approval for an indication broader than what was designated in its orphan drug application, it may not be entitled to exclusivity.

If a product designated as an orphan drug ultimately receives marketing approval for an indication broader

than what was designated in its orphan drug application, it may not be entitled to exclusivity.

Orphan drug exclusivity does not prevent the FDA from approving a different drug for the same disease or condition, or the same drug for a different disease or condition.

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Development in Pediatric Patients

Under the Pediatric Research Equity Act of 2003, a BLA or BLA supplement thereto must contain data that are adequate to assess the safety and effectiveness of the product for the claimed indications in all relevant pediatric subpopulations and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective.

A sponsor who is planning to submit a marketing application for a product that includes a new active ingredient, new indication, new

dosage form, new dosing regimen or new route of administration must submit a Pediatric Study Plan (“PSP”) that contains an outline of the proposed pediatric study or studies the applicant plans to conduct, including study objectives and design, any deferral or waiver requests and other information required by regulation.

Under the Pediatric Research Equity Act of 2003, a BLA, NDA or BLA supplement thereto must contain data that are adequate to assess the safety and effectiveness of the product for the claimed indications in all relevant pediatric subpopulations and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective.

A sponsor who is planning to submit a marketing application for a product that includes a new active ingredient, new indication, new dosage form, new dosing regimen or new route of administration must submit a Pediatric Study Plan (“PSP”) that contains an outline of the proposed pediatric study or studies the applicant plans to conduct, including study objectives and design, any deferral or waiver requests and other information required by regulation.

The sponsor and the FDA must reach agreement on the PSP.

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and, if granted, provides for the attachment of an additional six months of marketing protection to the term of any existing regulatory exclusivity, including orphan exclusivity.

This six-month exclusivity may be granted if a BLA sponsor submits pediatric data that fairly respond to a written request from the FDA for such data.

This six-month exclusivity may be granted if a BLA or NDA sponsor submits pediatric data that fairly respond to a written request from the FDA for such data.

The data do not need to show the product to be effective in the pediatric population studied;

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Biosimilars and Exclusivity

The ACA, which was signed into law in March 2010, included the BPCIA.

The Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act of 2010 (collectively the “ACA”), which was signed into law in March 2010, included the Biologics Price Competition and Innovation Act of 2009 (“BPCIA”).

The BPCIA established a regulatory scheme authorizing the FDA to approve biosimilars and interchangeable biosimilars.

A biosimilar is a biological product that is highly similar to an existing FDA-licensed “reference product.” Under the BPCIA, a manufacturer may submit an application for licensure of a biologic product that is “biosimilar to” or “interchangeable with” a previously approved biological product or “reference product.” In order for the FDA to approve a biosimilar product, it must find that there are no clinically meaningful differences between the reference product and proposed biosimilar product in terms of safety, purity and potency.

In order for the FDA to approve a biosimilar product, it must find that there are no clinically meaningful differences between the reference product and proposed biosimilar product in terms of safety, purity and potency.

For the FDA to approve a biosimilar product as interchangeable with a reference product, the agency must find that the biosimilar product can be expected to produce the same clinical results as the reference product in any given patient, and (for products administered multiple times to an individual) that the biologic and the reference biologic may be switched after one has been previously administered without increasing safety risks or risks of diminished efficacy relative to exclusive use of the reference biologic.

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Since the passage of the BPCIA, many states have passed laws or amendments to laws, including laws governing pharmacy practices, which are state regulated, to regulate the use of biosimilars.

Small Molecule Marketing Exclusivity

The FDCA provides a five-year period of non-patent marketing exclusivity within the United States to the first applicant to gain approval of an NDA for a new chemical entity.

A drug is a new chemical entity if the FDA has not previously approved any other new drug containing the same active moiety, which is the molecule or ion responsible for the action of the drug substance.

During the exclusivity period, the FDA may not accept for review an abbreviated new drug application ("ANDA") or a 505(b)(2) NDA submitted by another company for another version of such drug where the applicant does not own or have a legal right of reference to all the data required for approval.

However, an application may be submitted after four years if it contains a certification of patent invalidity or non-infringement.

The FDCA also provides three years of marketing exclusivity for an NDA, 505(b)(2) NDA, or supplement to an existing NDA if new clinical investigations, other than bioavailability studies, that were conducted or sponsored by the applicant are deemed by the FDA to be essential to the approval of the application.

Examples of applications that may require new clinical investigations essential to approval and receive three-year exclusivity include applications for new indications, dosages or strengths of an existing drug.

This three-year exclusivity covers only the conditions of use associated with the new clinical investigations and does not prohibit the FDA from approving ANDAs or 505(b)(2) NDAs for drugs containing the original active agent.

Five-year and three-year exclusivity will not delay the submission or approval of a full NDA.

applicant submitting a full NDA would be required to conduct or obtain a right of reference to all of the preclinical studies and adequate and well-controlled clinical trials necessary to demonstrate safety and effectiveness.

Patent Term Restoration and Extension

In the U.S., a patent claiming a new biologic product, its method of use or its method of manufacture may be eligible for a limited patent term extension under the Hatch-Waxman Amendments, which permits a patent extension of up to five years for patent term lost during product development and FDA regulatory review.

the ultimate approval date, except that the review period is reduced by any time during which the applicant failed to exercise due diligence.

Assuming grant of the patent for which the extension is sought, the restoration period for a patent covering a product is typically one-half the time between the effective date of the IND and the submission date of the BLA/NDA, plus the time between the submission date of the BLA/NDA and the ultimate approval date, except that the review period is reduced by any time during which the applicant failed to exercise due diligence.

Patent term restoration cannot be used to extend the remaining term of a patent past a total of 14 years from the product’s approval date in the U.S.

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Federal and State Data Privacy and Security Laws

Under HIPAA, HHS has issued regulations to protect the privacy and security of protected health information, used or disclosed by covered entities including certain healthcare providers, health plans and healthcare clearinghouses.

Under the Federal Health Insurance Portability and Accountability Act of 1996 (“HIPAA”), HHS has issued regulations to protect the privacy and security of protected health information, used or disclosed by covered entities including certain healthcare providers, health plans and healthcare clearinghouses.

HIPAA also regulates standardization of data content, codes and formats used in healthcare transactions and standardization of identifiers for health plans and providers.

HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009 or HITECH, and their regulations, including the final omnibus rule published on January 25, 2013, also imposes certain obligations on the business associates of covered entities and their covered subcontractors that obtain protected health information in providing services to or on behalf of covered entities or business associates.

HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009 (“HITECH”), and their regulations, including the final omnibus rule published on January 25, 2013, also imposes certain obligations on the business associates of covered entities and their covered subcontractors that obtain protected health information in providing services to or on behalf of covered entities or business associates.

In addition to federal privacy regulations, there are a number of state laws governing confidentiality and security of health information that are applicable to our business.

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Additionally, states, such as California, Virginia and Colorado have recently enacted the consumer privacy laws that grant rights to data subjects and place increased privacy and security obligations on entities handling personal data of consumers or households.

While we are not currently subject to laws such as the CCPA, some observers note that the CCPA and similar legislation could mark the beginning of a trend toward more stringent privacy legislation in the U.S., which could increase our potential liability and adversely affect our business.

While we are not currently subject to laws such as the California Consumer Privacy Act (“CCPA”), some observers note that the CCPA and similar legislation could mark the beginning of a trend toward more stringent privacy legislation in the U.S., which could increase our potential liability and adversely affect our business.

Because of the breadth of these laws and the narrowness of the statutory exceptions under such laws, it is possible that some of our current or future business activities, including certain clinical research, sales and marketing practices and the provision of certain items and services to our customers, could be subject to challenge under one or more of such privacy and data security laws.

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Data should be generated to demonstrate that a drug substance and a drug product can be manufactured and controlled according to the pre-specified quality standards.

The data relating to quality, preclinical testing and clinical trials should be submitted to the relevant competent authorities in a marketing authorization application (“MAA”) for regulatory review in order to determine whether a marketing authorization can be granted.

The data relating to quality, preclinical testing and clinical trials should be submitted to the relevant competent authorities in an MAA for regulatory review in order to determine whether a marketing authorization can be granted.

Even if a marketing authorization has been granted, there is a need to obtain a pricing and reimbursement decision before a new medicinal product can be marketed and sold in the EU and/or the UK (as applicable).

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The EU’s Priority Medicines (“PRIME”) scheme is intended to encourage drug development in areas of unmet medical need and facilitates accelerated assessment of medicinal products representing substantial innovation reviewed under the centralized procedure.

Eligible products must target conditions for which there is an unmet medical need (there is no satisfactory method of diagnosis, prevention or treatment in the EEA or, if there is, the new medicine will bring a major therapeutic advantage) and they must demonstrate the potential to address the unmet medical need by, for example, introducing new methods of therapy or improving existing ones.

Eligible products must target conditions for which there is an unmet medical need (there is no satisfactory method of diagnosis, prevention or treatment in the European Economic Area (“EEA”) or, if there is, the new medicine will bring a major therapeutic advantage) and they must demonstrate the potential to address the unmet medical need by, for example, introducing new methods of therapy or improving existing ones.

Products from small- and medium-sized enterprises may qualify for earlier entry into the PRIME scheme.

Many benefits accrue to sponsors of therapeutic candidates with PRIME designation, including but not limited to, early and proactive regulatory dialogue with the European Medicines Agency (“EMA”), frequent discussions on clinical trial designs and other development program elements, and accelerated MAA assessment once a dossier has been submitted.

Importantly, an EMA contact and rapporteur from the Committee for Human Medicinal Products (“CHMP”), or Committee for Advanced Therapies are appointed early in the PRIME scheme facilitating increased understanding of the product at the EMA’s Committee level.

Many benefits accrue to sponsors of therapeutic candidates with PRIME designation, including but not limited to, early and proactive regulatory dialogue with the EMA, frequent discussions on clinical trial designs and other development program elements, and accelerated MAA assessment once a dossier has been submitted.

Importantly, an EMA contact and rapporteur from the Committee for Human Medicinal

Products (“CHMP”), or Committee for Advanced Therapies are appointed early in the PRIME scheme facilitating increased understanding of the product at the EMA’s Committee level.

A kick-off meeting initiates these relationships and includes a team of multidisciplinary experts at the EMA to provide guidance on the overall development and regulatory strategies.

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The centralized procedure provides for the grant of a single marketing authorization by the European Commission that is valid for all EU member states, as well as the additional member states of the EEA (Norway, Iceland and Liechtenstein).

Pursuant to Regulation (EC) No 726/2004, the centralized procedure is compulsory for specific products, including for medicines developed by means of certain biotechnological processes (including, recombinant DNA technology, controlled expression of genes coding for biologically active proteins in prokaryotes and eukaryotes including transformed mammalian cells, and hybridoma and monoclonal antibody methods), products designated as orphan medicinal products, advanced therapy medicinal products (gene-therapy, somatic cell-therapy or tissue-engineered medicines) and products containing a new active substance indicated for the treatment of certain diseases, including products for the treatment of

cancer, HIV / AIDS, neurodegenerative disorders, diabetes, auto-immune diseases and other immune dysfunctions, and viral diseases.

The centralized procedure is optional for products containing a new active substance which was not authorized in the EU on May 20, 2004, or for products that constitute a significant therapeutic, scientific or technical innovation or which are in the interest of public health in the EU.

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Clock stops may extend the timeframe of evaluation of an MAA considerably beyond 210 days.

Where the CHMP gives a positive opinion, the EMA provides the opinion together with supporting documentation to the European Commission, who make the final decision to grant a marketing authorization, which is issued ordinarily within 67 days of receipt of the EMA’s recommendation.

Where the CHMP

gives a positive opinion, the EMA provides the opinion together with supporting documentation to the European Commission, who make the final decision to grant a marketing authorization, which is issued ordinarily within 67 days of receipt of the EMA’s recommendation.

Accelerated evaluation may be granted by the CHMP in exceptional cases, when a medicinal product is of major interest from the point of view of public health and, in particular, from the viewpoint of therapeutic innovation.

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However, centralized marketing authorizations no longer provide a valid basis for the commercialization of medicinal products in Great Britain.

Pursuant to the Windsor Framework, from January 1, 2025, all new medicinal products for the UK market will be authorized by the MHRA.

Pursuant to the Windsor Framework, from January 1, 2025, all new medicinal products for the UK market will be authorized by the Medicines and Healthcare Regulatory Agency (“MHRA”).

In this regard, the MHRA will grant a single UK-wide marketing authorization for all medicinal products intended for sale in the UK, enabling medicinal products to be sold in a single pack and under a single authorization throughout the UK.

Following its departure from the EU, the UK has introduced changes to its national licensing procedures, including procedures to prioritize access to new medicines that will benefit patients, ILAP (described above) and new routes of evaluation for novel products and biotechnological products.

Notwithstanding that there is no wholesale recognition of EU pharmaceutical legislation under the TCA, and that EU marketing authorizations do not automatically provide a valid basis for the commercialization of medicinal products in Great Britain from January 1, 2024, applicants will be able to request the MHRA to recognize marketing authorizations granted in foreign jurisdictions (including the EU) under a new International Recognition Procedure.

Notwithstanding that there is no wholesale recognition of EU pharmaceutical legislation under the Trade and Cooperation Agreement (“TCA”), and that EU marketing authorizations do not automatically provide a valid basis for the commercialization of medicinal products in Great Britain from January 1, 2024, applicants will be able to request the MHRA to recognize marketing authorizations granted in foreign jurisdictions (including the EU) under a new International Recognition Procedure.

Regulatory Data Protection in Europe

In the EU and the UK, new chemical entities (including both small molecules and biological medicinal products) and new biological substances approved on the basis of a complete independent data package consisting of quality, preclinical testing results and clinical trial data qualify for eight years of RDP upon grant of a marketing authorization and two years of marketing protection.

In the EU and the UK, new chemical entities (including both small molecules and biological medicinal products) and new biological substances approved on the basis of a complete independent data package consisting of quality, preclinical testing results and clinical trial data qualify for eight years of Regulatory Data Protection (“RDP”) upon grant of a marketing authorization and two years of marketing protection.

Data protection prevents generic or biosimilar applicants from referencing the innovator’s preclinical and clinical trial data contained in the MAA dossier of the reference medicinal product when applying for a generic or biosimilar marketing authorization, for a period of eight years from the date on which the reference product was first authorized in the EU.

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Even if a generic or biosimilar medicinal product is approved, it cannot be marketed until the expiration of the marketing protection.

The ten-year protection period can be extended to a maximum of eleven years if, during the first eight years of those ten years, the marketing authorization holder obtains an authorization for one or more new therapeutic indications which, during the scientific evaluation prior to authorization, is

held to bring a significant clinical benefit in comparison with existing therapies.

Even if a compound is considered to be a new chemical or a new biological entity so that the innovator gains the prescribed period of data protection, another company may market another version of the medicinal product if such company obtained marketing authorization based on an MAA with a complete and independent data package consisting of pharmaceutical and preclinical testing results and clinical trial data.

Patent Term Extensions in the EU and Other Jurisdictions

The EU also provides for patent term extension through SPCs which aim to offset the loss of patent protection for pharmaceutical products arising from the lengthy testing and clinical trials required to obtain an MA.

The EU also provides for patent term extension through Supplementary Protection Certificate (“SPCs”) which aim to offset the loss of patent protection for pharmaceutical products arising from the lengthy testing and clinical trials required to obtain an MA.

The rules and requirements for obtaining a SPC are similar to those in the U.S.

An SPC may extend the term of a basic patent for up to five years after its originally scheduled expiration date in order to provide up to a maximum of fifteen years of exclusivity from the time the medicinal product in question first obtains an MA for it to be placed on the market.

An SPC may extend the

term of a basic patent for up to five years after its originally scheduled expiration date in order to provide up to a maximum of fifteen years of exclusivity from the time the medicinal product in question first obtains an MA for it to be placed on the market.

As mentioned above, in certain circumstances, these periods may be extended for six additional months if pediatric exclusivity is obtained;

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The processing of personal data regarding individuals in the EU, including personal health data, is regulated by Regulation (EU) 2016/679, which took effect on May 25, 2018.

The GDPR is wide-ranging in scope and imposes numerous requirements on companies that process personal data, including requirements relating to processing health and other sensitive data, obtaining consent of the individuals to whom the personal data relates, providing information to individuals

regarding data processing activities, implementing safeguards to protect the security and confidentiality of personal data, providing notification of data breaches and taking certain measures when engaging third-party processors.

The General Data Protection Regulation (“GDPR”) is wide-ranging in scope and imposes numerous requirements on companies that process personal data, including requirements relating to processing health and other sensitive data, obtaining consent of the individuals to whom the personal data relates, providing information to individuals regarding data processing activities, implementing safeguards to protect the security and confidentiality of personal data, providing notification of data breaches and taking certain measures when engaging third-party processors.

The GDPR also imposes strict rules on the transfer of personal data to countries outside the EU, including the U.S., and permits data protection authorities to impose large penalties for violations of the GDPR, including potential fines of up to €20 million or 4% of annual global revenues, whichever is greater.

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As of January 1, 2021, the UK’s European Union (Withdrawal) Act 2018 incorporated the GDPR (as it existed on December 31, 2020 but subject to certain UK specific amendments) into UK law, referred to as the UK GDPR.

The UK GDPR and the UK Data Protection Act 2018 set out the UK’s data protection regime, which is independent from but aligned to the EU’s data protection regime.

The UK GDPR and the UK Data Protection Act 2018 set out the UK’s data protection regime, which is independent from but

aligned to the EU’s data protection regime.

Non-compliance with the UK GDPR may result in monetary penalties of up to £17.5 million or 4% of worldwide revenue, whichever is higher.

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More generally, price concessions may need to be offered to third party payors to obtain favorable coverage or to purchasers to achieve sales.

Hospitals and health systems are increasingly using bidding procedures to determine what pharmaceutical products and which suppliers will be included in their prescription drug and other healthcare programs.

Arrangements with third party payors or purchasers may include value-based arrangements under which the amount paid for products depends on the performance of the product.

Net prices for drugs may be further 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.

Net prices for drugs may be further reduced 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.

In addition, in some foreign countries, the proposed pricing for a drug must be approved before it may be lawfully marketed.

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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 EU do not follow price structures of the U.S.

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In both the U.S.

and certain foreign jurisdictions, there have been a number of legislative and regulatory changes to the healthcare system that could impact our ability to sell our product candidates profitably if and when approved for marketing.

In particular, in 2010, the ACA was enacted, which, among other things, subjected biologic products to potential competition by lower-cost biosimilars;

and certain foreign jurisdictions, there have been a number of reforms to the healthcare system that could impact our ability to sell our product candidates profitably if and when approved for marketing.

For example, in 2010, the ACA was enacted, which, among other things, subjected biologic products to potential competition by lower-cost biosimilars;

addressed a new methodology by which rebates owed by manufacturers under the Medicaid Drug Rebate Program are calculated for drugs that are inhaled, infused, instilled, implanted or injected;

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created a new Medicare Part D coverage gap discount program, in which manufacturers must agree to offer point-of-sale discounts off negotiated prices of applicable brand drugs to eligible beneficiaries during their coverage gap period, as a condition for the manufacturer’s outpatient drugs to be covered under Medicare Part D.

More generally, the ACA expanded healthcare coverage through Medicaid expansion and the implementation of the “individual mandate” for health insurance coverage.

Beyond the ACA, there have been ongoing healthcare reform efforts.

Drug pricing and payment reform was a focus of the Trump administration and has been a focus of the Biden administration.

For example, federal legislation enacted in 2021 eliminates the statutory cap on Medicaid drug rebate program rebates (currently set at 100% of a drug’s “average manufacturer price”), effective January 1, 2024.

As another example, the IRA, includes a number of changes intended to address rising prescription drug prices in Medicare Parts B and D.

These changes include caps on Medicare Part D out-of-pocket costs, Medicare Part B and Part D drug price inflation rebates, a new Medicare Part D manufacturer discount drug program (replacing the ACA Medicare Part D coverage gap discount program) and a drug price negotiation program for certain high spend Medicare Part B and D drugs (with the first list of drugs announced in 2023).

The IRA changes have varying implementation dates that start in 2022.

On August 29, 2023, HHS announced the list of the first ten drugs that will be subject to price negotiations.

The focus on healthcare reform, including reform of drug pricing and payment, has continued in the wake of the IRA.

For example, in 2022, subsequent to the enactment of the IRA, the Biden administration released an executive order directing the HHS to report on how the Center for Medicare and Medicaid Innovation (“CMMI”) could be leveraged to test new models for lowering drug costs for Medicare and Medicaid beneficiaries.

The report was issued in 2023 and proposed various models that CMMI is currently developing which seek to lower the cost of drugs, promote accessibility and improve quality of care.

Further, in December 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 (which allow the government, in specified circumstances, to grant or require a patent-holder of technology funded by the federal government to grant a license to certain third parties).

The announcement was followed by publication of 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, given these actions, there can be no certainty that such rights will not be exercised in the future.

Healthcare reform efforts have been and may continue to be subject to scrutiny and legal challenge.

For example, with respect to the ACA, tax reform legislation was enacted that eliminated the tax penalty established for individuals who do not maintain mandated health insurance coverage beginning in 2019 and, in 2021, the U.S.

Supreme Court dismissed the latest judicial challenge to the ACA brought by several states without specifically ruling on the constitutionality of the ACA.

As another example, revisions to regulations under the federal anti-kickback statute would remove protection for traditional Medicare Part D discounts offered by pharmaceutical manufacturers to pharmacy benefit managers and health plans.

Pursuant to court order, the removal was delayed and recent legislation imposed a moratorium on implementation of the rule until January 2032.

As another example, the IRA drug price negotiation program has been challenged in litigation filed by various pharmaceutical manufacturers and industry groups.

Beyond the ACA, there have been ongoing healthcare reform efforts, including efforts focused on drug pricing and payment.

For example, the Inflation Reduction Act (“IRA”), includes a number of changes intended to address rising prescription drug prices in Medicare Parts B and D.

The IRA has had and will likely continue to have a significant impact on the pharmaceutical industry.

Additionally, changes to Medicaid effective in 2024 eliminated the Medicaid rebate cap and changes to certain Medicare price reporting requirements for drugs beginning in 2026 will likely increase the administrative and compliance burden for manufacturers.

Recently, drug pricing and payment has been subject to a number of reform initiatives.

For example, the current presidential administration issued an Executive Order in April 2025 with multiple directives aimed at lowering drug prices, including refining the Medicare drug price negotiation program established by the IRA;

accelerating competition for high-cost prescription drugs by accelerating approval of generics and biosimilars and facilitating the process for re-classifying prescription drugs as over-the-counter drugs;

and increasing drug importation.

In May 2025, the current presidential administration issued another Executive Order that directed government agencies and officials to identify most-favored nation pricing targets for prescription drugs (and looked to pharmaceutical manufacturers to make significant progress towards delivering target prices to patients);

prevent foreign countries from disproportionately shifting the cost of global pharmaceutical research and development to the United States;

and facilitate direct-to-consumer purchasing programs for pharmaceutical manufacturers to sell their products to patients at the most-favored-nation price.

In the wake of the Executive Orders and related executive initiatives, a number of pharmaceutical manufacturers have announced direct-to-consumer offerings with discounted prices and/or reached agreement with the federal government regarding pricing for drugs, including prices for Medicaid drugs and newly launched products.

A website sponsored by the federal government offering pharmaceutical direct-to-consumer channels has also been launched.

Federal agencies are developing new drug pricing pilot programs, such as a voluntary Medicaid initiative which would authorize the federal government to negotiate Medicaid supplemental rebates with participating manufacturers on behalf of state Medicaid programs, in exchange for standardized coverage criteria for participating manufacturer drugs, and proposed Medicare Part B and Part D pilot models that, if finalized as proposed, would replace existing inflation-based Medicare rebates with rebates determined on the basis of international prices, for drugs and patients subject to the model.

Many of these reform initiatives would require additional legal and/or administrative action to implement and may be subject to legal challenge.

Other federal healthcare reform efforts or actions may affect access to healthcare coverage or the funding of health care benefits, although the full impact of such efforts or actions cannot be predicted.

For example, the Congressional Budget Office has estimated that Medicaid provisions in the 2025 budget reconciliation legislation, including restrictions in eligibility and funding for Medicaid, as well as changes to the healthcare marketplace such as the elimination of certain subsidies, will increase the number of uninsured.

There have also been efforts by federal and state government officials or legislators to implement measures to regulate prices or payment for pharmaceutical products, including legislation on drug importation.

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It is unclear how this program will be implemented, including which drugs will be chosen, and whether it will be subject to legal challenges in the U.S.

Other states have also submitted Section 804 Importation Program (“SIP”) proposals that are pending review by the FDA.

Other states have also submitted SIP proposals that are pending review by the FDA.

Any such approved importation plans, when implemented, may result in lower drug prices for products covered by those programs.

Recently, there has been considerable public and government scrutiny of pharmaceutical pricing and proposals to address the perceived high cost of pharmaceuticals.

There have also been recent state legislative efforts to address drug costs, which generally have focused on increasing transparency around drug costs or limiting drug prices.

General legislative cost control measures may also affect reimbursement for our product candidates.

The Budget Control Act, as amended, resulted in the imposition of reductions in Medicare (but not Medicaid) payments to providers in 2013 that remain in effect through 2032 unless additional Congressional action is taken.

At the state level, individual states are increasingly implementing initiatives designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and measures to encourage importation from other countries and bulk purchasing.

For example, certain states have formed Prescription Drug Affordability Boards that assert authority to set reimbursement rates and/or drug pricing in the state.

States are also increasingly expanding or changing Medicaid supplemental rebate programs to secure additional rebates from manufacturers in exchange for drug coverage and to limit coverage of certain drugs for certain Medicaid patients or to all Medicaid patients.

These and other future state-level reform activities could negatively affect Medicaid coverage and reimbursement for our products.

Healthcare reform efforts have been and may continue to be subject to scrutiny, legal challenge and subsequent amendment, creating further uncertainty.

Other recent government actions may also affect prices or payments for prescription drugs.

For example, the Trump Administration’s recently announced tariff on branded or patented drugs may increase the cost of drug products that are imported from abroad or manufactured using products or materials imported from abroad.

The timeline for implementation of this tariff has not yet been finalized.

As another example, the Budget Control Act, as amended (the “Budget Control Act”), resulted in the imposition of reductions in Medicare (but not Medicaid) payments to providers in 2013 that remain in effect through 2032 unless additional Congressional action is taken.

Any significant spending reductions affecting Medicare, Medicaid or other publicly funded or subsidized health programs that may be implemented and/or any significant taxes or fees that may be imposed on us could have an adverse impact on our results of operations.

Adoption of new legislation at the federal or state level could affect demand for, or pricing of, any future products if approved for sale.

We cannot, however, predict the ultimate content, timing or effect of any federal and state reform efforts.

There is no assurance that federal or state healthcare reform will not adversely affect our future business and financial results.

Future healthcare or related reforms could affect demand for, or pricing of, any future products if approved for sale.

We cannot, however, predict the ultimate content, timing or effect of any reform efforts.

There is no assurance that such reform will not adversely affect our future business and financial results.

Other Healthcare Laws

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● the FDCA, which among other things, strictly regulates drug marketing, prohibits manufacturers from marketing such products for off-label use and regulates the distribution of samples;

● federal laws that require pharmaceutical manufacturers to report certain calculated product prices to the government or provide certain discounts or rebates to government authorities or private entities, often as a condition of reimbursement under government healthcare programs;

● federal laws that require pharmaceutical manufacturers to calculate, certify and report certain complex calculated product prices to the government or provide certain discounts or rebates to government authorities or private entities, often as a condition of reimbursement under government healthcare programs;

● the so-called “federal sunshine” law, which requires pharmaceutical and medical device companies to monitor and report certain financial interactions with physicians, certain non-physician practitioners and teaching hospitals to the federal government for re-disclosure to the public;

Foreign Corrupt Practices Act of 1977, as amended, which prohibits, among other things, U.S.

Foreign Corrupt Practices Act of 1977, as amended (the “FCPA”), which prohibits, among other things, U.S.

companies and their employees and agents from authorizing, promising, offering, or providing, directly or indirectly, corrupt or improper payments or anything else of value to foreign government officials, employees of public international organizations and foreign government owned or affiliated entities, candidates for foreign political office, and foreign political parties or officials thereof;

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Our compensation program is designed to retain, motivate and attract highly qualified employees.

Accordingly, we

use a mix of competitive base salary, cash-based annual incentive compensation, performance-based equity compensation awards and other employee benefits.

Accordingly, we use a mix of competitive base salary, cash-based annual incentive compensation, performance-based equity compensation awards and other employee benefits.

● Health and safety :

We value the health and safety of our employees and provide comprehensive insurance benefits, an employee assistance program, paid holidays, a personal time-off program, and other benefits which are intended to assist employees to manage their well-being.

● Inclusion and diversity :

We are committed to efforts to increase diversity and foster an inclusive professional environment that supports our workforce.

● Inclusion :

We are committed to efforts to foster an inclusive professional environment that supports our workforce.

Corporate and Other Information

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On August 2, 2023, the Company (then known as Zenas BioPharma (Cayman) Limited) de-registered from the Cayman Islands and registered by way of continuation in the State of Delaware.

Our common stock currently trades on the Nasdaq Global Select Market under the ticker symbol “ZBIO”.

Our principal executive offices are located at 852 Winter Street, Suite 250, Waltham MA 02451, and our telephone number at that address is (857) 271-2954.

On September 16, 2024, the Company completed its initial public offering (“IPO”), in which the Company issued and sold 15,220,588 shares of its common stock, including 1,985,294 shares pursuant to the full exercise of the underwriters’ option to purchase additional shares, at a public offering price of $17.00 per share, for aggregate gross proceeds of $258.7 million.

The Company received approximately $234.3 million in net proceeds after deducting underwriting discounts, commissions and other offering expenses.

Available Information

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Our website and the information contained on, or that can be accessed through, the website will not be deemed to be incorporated by reference in, and are not considered part of, this Annual Report on Form 10-K.

We have included our website in this Annual Report solely as an inactive textual reference.

Our Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K, including exhibits, proxy and information statements and amendments to those reports filed or furnished pursuant to Sections 13(a), 14, and 15(d) of the Securities Exchange Act of 1934, as amended (the “Exchange Act”) are available through the “Investor & Media Relations” portion of our website free of charge as soon as reasonably practicable after we electronically file such material with, or furnish it to, the SEC.

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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