What changed in this filing

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Item 1. Business

2025-03-18 compared with 2024-03-15 · 33 added, 37 removed, 77 unchanged (48% of the section changed)

20 unchanged sentences

stroke), IL-1a may mediate harmful disease-related activity.

At the end of 2019, XBiotech sold a True Human™ antibody therapeutic it was developing that targeted IL-1a for $1.35 billion in cash and potential milestone payments.

With the unique deal structure XBiotech agreed to not develop any anti-IL-1a antibodies for dermatology, while XBiotech remained free to continue to discover and develop new True Human™ anti-IL-1a antibodies for use in areas of medicine outside of dermatology.

The Company quickly identified new IL-1a targeting product candidates that it is has already brought into clinical studies in oncology, rheumatology and neurology.

While the Company previously was focused on a single True Human™ antibody targeting IL-1a, it is now developing in parallel two anti-IL-1a product candidates and may develop one or more others.

At the end of 2019, XBiotech sold a True Human TM antibody therapeutic it was developing that targeted IL-1a for $750 million in cash and $600 million potential milestone payments.

In a unique deal structure, XBiotech agreed to not further develop any anti-IL-1a antibodies for dermatology, while XBiotech remained free to discover and develop new True Human TM anti-IL-1a antibodies for use in areas of medicine outside of dermatology.

The Company quickly identified new IL-1a targeting product candidates and has already brought these into clinical studies under INDs in oncology, rheumatology and neurology.

While the Company previously was focused on a single True Human TM antibody targeting IL-1a, it is now developing in parallel two anti-IL-1a product candidates and may develop one or more others.

Since IL-1a is involved in the pathology of multiple diseases, it makes business sense to use different anti-IL-1a antibodies for specific areas of medicine, allowing potential partnership or sale of each antibody separately for different disease indications.

XBiotech's sale of its True Human™ antibody Bermekimab generated a total $750 million in income between December 30, 2019 and June 30, 2021.

XBiotech’s sale of its True Human TM antibody Bermekimab generated a total $750 million in income between December 30, 2019 and June 30, 2021.

Since 2020, the Company has returned a total of $495 million to its shareholders through a combination of stock repurchase and dividends.

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In 2022 XBiotech extended the supply agreement.

As of March 2024, these agreements have now come to a successful conclusion and as of March 2024 XBiotech is no longer producing drug product or conducting contract clinical research.

As of the end of 2023, these agreements have come to a successful conclusion and XBiotech is no longer producing drug product or conducting contract clinical research under these agreements.

Development of IL-1 a Therapies

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In 2021, the Company commenced a clinical study with its Natrunix™ True Human™ antibody targeting IL-1⍺ in oncology (Pancreatic Cancer).

The study is randomized, placebo controlled to provide a preliminary assessment of efficacy and safety for Natrunix in combination with chemotherapy in an advanced cancer population.

The study was randomized, double-blinded and placebo controlled to provide a preliminary assessment of efficacy and safety for Natrunix in combination with chemotherapy in an advanced cancer population.

The study was sized to include 60 subjects, intended to provide a preliminary assessment of efficacy.

The last subject in the study had their last visit in February 2024.

Data collection is therefore now complete.

Over approximately the next six weeks, clinical monitors will perform visitations across the United States at clinical sites that enrolled subjects into the study.

During these visits monitors will review source data to make sure all data has been properly recorded and upon satisfactory completion of the review, sites will be officially closed.

When this process is complete, the database will be locked and data analyzed according to protocol.

Reporting on results for the pancreatic cancer study are expected within several weeks of data lock.

The Company started a clinical program in Rheumatology in August, 2023 with a 210 patient study in rheumatoid arthritis.

This double blind, placebo controlled study is investigating the efficacy of Natrunix as a treatment for rheumatoid arthritis in combination with the common prescription medication methotrexate.

As of March 2024, the study has enrolled in about half of the subjects, with at least six months remaining until the last subject is taken into the program.

The study aims to demonstrate that Natrunix will not only significantly enhance treatment outcomes of subjects already taking methotrexate, but that Natrunix will also reduce some of the side effects associated with Methotrexate.

The Company is planning to launch additional studies in rheumatology during Q2 2024.

The last subject in the study had their last visit in February 2024 and only a single subject remains in the study under a provision for indefinite open label extension.

Database lock was performed and an announcement of the preliminary analysis of the data was made June 18, 2024.

The company believes the findings from the study represent a transformative approach to cancer management.

Subjects treated with Natrunix had reduced hospitalization, fewer serious adverse events, longer periods of progression free survival and less incidence of severe diarhea, compared to patients receiving placebo.

The company further believes that the treatment effect is not specific to pancreatic cancer, and a similar effect may be seen in other solid tumors being treated with chemotherapy.

An analagous therapy is G-CSF, originally developed by Amgen and approved in 1991.

The therapy helped recovery of patients undergoing myelosuppressive chemotherapy and has been widely used ever since as an adjunct.

The Company has been carefully considering an FDA regulatory path based on historical approvals and plans to present its findings and propose a registration path to the FDA in the second quarter 2025.

The Company launched a clinical Rheumatology program in August, 2023.

A total of 233 subjects were enrolled into a double blind, placebo controlled study to investigate the efficacy of Natrunix as a treatment for rheumatoid arthritis in combination with a common prescription medication, methotrexate.

The study was completed and an announcement of findings were made on December 23, 2024.

The study aimed to demonstrate that Natrunix would significantly enhance treatment outcomes with reduced side effects of subjects already taking methotrexate.

However, numerous enrollment irregularities were observed with major enrolling clinical sites.

Further investigation of the sites led the Company to believe that widespread improprieties at clinical sites render the data uninterpretable.

The Company continues to believe in the potential for Natrunix as a treatment for arthritic diseases.

XBiotech filed an investigational new drug application in 2022 for our True Human™ antibody Hutrukin.

Hutrukin is a candidate breakthrough therapeutic that is being evaluated for its ability to reduce brain injury that occurs after reperfusion procedures used to treat stroke.

Hutrukin is a candidate therapeutic to reduce brain injury that occurs after reperfusion procedures used to treat stroke.

The Company completed a phase I study at the end of 2023 that demonstrated high bolus doses of Hutrukin, similar to doses that would be given to prevent brain reperfusion injury in stroke therapy, are safe and well tolerated.

Analysis of the data from the Phase I study is expected to be completed in Q1 2024.

However, no significant adverse events were noted during the study and the data analysis is expected to be positive.

The Company is planning a Phase II study in stroke during 2024.

Ischemic stroke which accounts for some 87% of strokes, is a leading cause of mortality and serious long-term disability worldwide.

For decades the medical approach has been to unblock the affected artery and return blood supply to the brain.

It was intuitive that opening the occluded artery to return blood supply, or “reperfuse” the ischemic brain would lead to better outcomes for stroke victims.

This expectation was not in fact supported by clinical observations.

Clinical studies have shown that in reality, reperfusion of the affected brain is associated with ongoing irreparable damage to ischemic tissue that, prior to reperfusion, appears viable by both physical and metabolic assessments.

The necrotic infarct core that results from a stroke has been found to increase in size upon reperfusion, seemingly as a result of the resumption of enhanced blood supply.

Hutrukin may reduce the likelihood of inflammation-related secondary injury after ischemia by disrupting the molecular pathways which activate leukocyte migration and infiltration.

Leukocyte migration and infiltration into the ischemic regions of the brain after reperfusion may mediate damage seen after reperfusion.

Clinical studies with Hutrukin will be aimed at demonstrating a reduction of reperfusion injury and improved outcomes in stroke victims.

Analysis of the data was completed in Q1 2024.

The Company’s plan to launch a Phase II study in stroke during 2024 was put on hold until its regulatory path for its cancer and arthritis programs are clarified with the FDA.

Infectious Disease Pipeline

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True Human™ antibodies are derived only from donors who we have found to have the best disease fighting antibodies in that populations.

True Human™ antibodies may be used to provide highly potent and targeted immunity against infectious diseases, including:

in the elderly, where natural immunity is waning;

True Human™ antibodies may be used to provide highly potent and targeted immunity against infectious diseases, including in the elderly, where natural immunity is waning;

in young children where immunity has yet to develop;

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The expansion resulted in the creation of two new wings:

one provides state-of-the-art research laboratory for scientists;

one provides state-of-the-art research laboratory for R&D scientists;

another area provides administrative space for dozens of personnel working in manufacturing, clinical and other operations.

The building additions have enhanced the Company’s ability to house a larger workforce, expand R&D activities and orchestrate the production of multiple drug products from its existing manufacturing and R&D center.

In Q1 2024 the Company re-launched its program to construct a new multi-story 46,000 ft 2 research and development facility and a 5,000 ft 2 infectious disease research annex, to further enhance the Company’s discovery and product development capabilities.

Both the multi-story complex and research annex will be located on the Company’s 48 acre campus adjacent to the existing R&D center.

In Q1 2024, XBiotech began drawing detailed architectural and engineering plans and submitting requests for City permits to construct a new multi-story 46,000 ft 2 research and development facility and a 5,000 ft 2 infectious disease research annex.

The project was in anticipation of rapid growth in clinical operations and other areas of operations.

Regulatory and other setbacks in the rheumatology program have pushed back the timing for the increased infrastructure needs.

Construction of both the multi-story complex and research annex has been indefinitely paused.

The Company continues to pursue complete City permitting for the expansion so that construction may commence without delay at the appropriate timing.

A Background on Therapeutic Antibodies

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Our board of directors (“Board”) is constituted by individuals with significant industry, scientific and legal knowledge.

As of December 31, 2023, we had 82 full-time employees.

As of December 31, 2024, we had 92 total employees, each of which is a full-time employee.

None of our employees are represented by a collective bargaining agreement, nor have we experienced any work stoppage.

9 unchanged sentences

Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business