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Item 1. Business

2024-03-11 compared with 2023-03-01 · 187 added, 252 removed, 367 unchanged (54% of the section changed)

We are a clinical-stage biotechnology company focused on delivering innovative immunology therapeutics.

We are developing immune cell modulating antibodies, including two wholly owned checkpoint agonists in clinical-stage development, for autoimmune and inflammatory disease:

rosnilimab, our PD-1 agonist, previously referred to as ANB030, in a planned Phase 2b trial for the treatment of moderate-to-severe rheumatoid arthritis (“RA”);

and ANB032, our BTLA agonist, in a planned Phase 2b trial for the treatment of moderate-to-severe atopic dermatitis (“AD”).

We also have other preclinical immune cell modulator candidates in our portfolio, including ANB033, an anti-CD122 antagonist antibody for the treatment of autoimmune and inflammatory diseases.

In addition, we have two cytokine antagonists that we are exploring options for out-licensing:

imsidolimab, our anti-IL-36R antibody, in a Phase 3 trial for the treatment of generalized pustular psoriasis (“GPP”), and etokimab, our anti-IL-33 antagonist that is Phase 2/3 ready.

We are developing immune cell modulating antibodies, including two wholly owned checkpoint agonists in clinical-stage development, for autoimmune and inflammatory diseases:

rosnilimab, our PD-1 agonist in a Phase 2b trial for the treatment of moderate-to-severe rheumatoid arthritis (“RA”) and a Phase 2 trial for the treatment of moderate-to-severe ulcerative colitis (“UC”);

and ANB032, our BTLA agonist, in a Phase 2b trial for the treatment of moderate-to-severe atopic dermatitis (“AD”).

We also have other preclinical immune cell modulator candidates for the treatment of autoimmune and inflammatory diseases in our portfolio, including ANB033, an anti-CD122 antagonist antibody, and ANB101, a BDCA2 modulator antibody.

In addition, we have developed two cytokine antagonists that we are exploring options for out-licensing:

imsidolimab, our anti-IL-36R antibody, in Phase 3 development for the treatment of generalized pustular psoriasis (“GPP”), and etokimab, our anti-IL-33 antagonist that is Phase 2/3 ready.

We have also discovered multiple therapeutic antibodies licensed to GlaxoSmithKline, Inc.

(“GSK”) in a financial collaboration for immune-oncology, including an anti-PD-1 antagonist antibody (JEMPERLI (dostarlimab-gxly)), an anti-TIM-3 antagonist antibody (cobolimab, GSK4069889) and an anti-LAG-3 antagonist antibody (GSK4074386).

(“GSK”) in a financial collaboration for immuno-oncology, including an anti-PD-1 antagonist antibody ( Jemperli (dostarlimab-gxly)) and an anti-TIM-3 antagonist antibody (cobolimab, GSK4069889).

We currently recognize revenue from milestones and royalties achieved under our immuno-oncology collaboration with GSK.

Our Wholly Owned Product Candidate Pipeline

Our immune cell modulating antibodies, including anti-inflammatory checkpoint agonists for PD-1 and BTLA, treat inflammatory disorders by down regulating immune responses mediated by multiple immune cell types including T-cells, B-cells, and dendritic cells.

We believe these molecules have potential applicability across a broad range of autoimmune and inflammatory disorders including dermatology, rheumatology, gastroenterology, respiratory, and neurology therapeutic areas.

Rosnilimab is designed to suppress aberrant T cell driven inflammation by augmenting signaling through PD-1 or targeted depletion of PD-1+ T cells.

Rosnilimab binds to PD-1 on a membrane proximal epitope that is on the opposite side of the receptor to that utilized by PD-L1 for binding, and thus preserves the ability of PD-L1 to agonize PD-1.

In the setting of T cell activation, rosnilimab binding has been shown to induce agonistic signaling and the recruitment of SHP2 to PD-1, in a manner similar to that by PD-L1.

In preclinical assays, rosnilimab prevented T cell expansion in antigen-specific response assays to numerous antigens, demonstrating prevention of T cell expansion and reduction in the secretion of inflammatory cytokines associated with multiple T cell types implicated in inflammatory pathology when dysregulated.

In addition to direct agonistic activity, rosnilimab is an IgG1k antibody with effector function that can drive targeted depletion of PD-1+ T cells via the induction of antibody-dependent cellular cytotoxicity (ADCC).

We believe this component of the mechanism of rosnilimab may provide more durable immune modulation by effectively eliminating the most pathogenic antigen-specific T cells in the setting of autoimmunity and inflammation.

Genetic mutations in the PD-1 pathway are known to be associated with increased susceptibility to human inflammatory diseases, and hence we believe that rosnilimab is applicable to diseases where PD-1 checkpoint receptor function may be insufficient to maintain immune homeostasis.

Our immune cell modulating antibodies, including checkpoint agonists for PD-1 and BTLA, treat inflammatory disorders by down regulating immune responses mediated by multiple immune cell types including T cells, B cells, and dendritic cells.

T cells require both antigen presentation to the T cell receptor and co-stimulation to be activated.

When these interactions are inhibited, T cells can’t be effectively primed to expand and differentiate into inflammatory T cells.

Inhibition of at least one of these signals is the basis of checkpoint agonism.

We believe these molecules have potential applicability across a broad range of autoimmune and inflammatory diseases, including dermatology, rheumatology, gastroenterology, respiratory, and neurology therapeutic areas.

PD-1, or programmed cell death protein 1, is an inhibitory checkpoint receptor that regulates T cell proliferation, and cytokine secretion.

It is expressed preferentially on activated T cells, reducing the potential for off-target activity by rosnilimab.

Genetic mutations in the PD-1 pathway are known to be associated with increased susceptibility to human inflammatory diseases which leads us to believe that rosnilimab is applicable to diseases where PD-1 checkpoint receptor function may be insufficient to maintain immune homeostasis.

Rosnilimab is an IgG1 antibody that directly targets PD-1+ T cells, resulting in their agonism or depletion, broadly impacting pathogenic drivers of autoimmune and inflammatory diseases.

An IgG1 PD-1 agonist acts through three distinct mechanisms:

depletion of PD-1 high effector T cells, depletion of PD-1 high Tfh and Tph cells, and agonism of PD-1 int T cells.

This drives specific immunological outcomes in both inflamed tissue and the periphery, such as reduction in T cell proliferation, migration, and cytokine secretion, and reduction of plasma cell generation and autoantibody levels.

Rosnilimab is designed to enable formation of a tight immune synapse by binding to the PD-1 checkpoint receptor on a membrane-proximal epitope, and simultaneously anchoring to an Fc receptor, on an opposing cell, supporting crosslinking and excluding activating phosphatases such as CD45.

Rosnilimab also facilitates depletion by bringing effector cells into closer proximity to pathogenically activated PD-1 high T cells.

In in vitro studies, when PD-1+ T cells were cocultured in the presence of NK cells, rosnilimab demonstrated potent depletion of PD-1+ T cells.

In separate in vitro studies, in which T cells were stimulated in the presence of only dendritic cells (in the absence of any cells capable of mediating depletion), rosnilimab demonstrated potent agonism properties such as a reduction in PD-1+T cell proliferation and reduction in secretion of inflammatory cytokines.

We announced positive top-line data from a healthy volunteer Phase 1 trial of rosnilimab in November 2021.

A total of 144 subjects were enrolled in the randomized, double-blind, placebo-controlled healthy volunteer Phase 1 trial, where single ascending dose (SAD) cohorts were administered single subcutaneous or intravenous (“IV”) doses of rosnilimab up to 600mg or placebo, while multiple ascending dose (MAD) cohorts received four weekly subcutaneous doses of rosnilimab ranging up to 400mg or placebo.

A total of 144 subjects were enrolled in the randomized, double-blind, placebo-controlled healthy volunteer Phase 1 trial, where single ascending dose (“SAD”) cohorts received subcutaneous or intravenous (“IV”) single doses of rosnilimab up to 600mg or placebo, while multiple ascending dose (“MAD”) cohorts received four weekly subcutaneous doses of rosnilimab ranging up to 400mg or placebo.

Rosnilimab was generally well-tolerated and no dose limiting toxicities were observed.

Two serious adverse events were reported in single dose cohorts, including obstructive pancreatitis in a placebo-dosed subject and COVID-19 infection in a rosnilimab-dosed subject leading to discontinuation.

Two serious adverse events (“SAEs”) were reported in single dose cohorts, including obstructive pancreatitis in a placebo-dosed subject and COVID-19 infection in a rosnilimab-dosed subject leading to discontinuation.

The COVID-19 infection was deemed unrelated to treatment.

No serious adverse events were reported in subjects receiving multiple doses of rosnilimab or placebo.

Rosnilimab demonstrated a favorable pharmacokinetic profile with an estimated two-week half-life for subcutaneous and IV routes of administration.

Full PD-1 receptor occupancy was observed rapidly and was maintained for at least 30 days at or above 200mg following single subcutaneous rosnilimab doses.

Rosnilimab pharmacodynamic activity demonstrated rapid and sustained reduction in the quantity and functional activity of PD-1+ T cells, which are known to be pathogenic drivers of inflammatory diseases.

Conventional T (Tcon) cells (CD3+, CD25 low) PD-1+, which represented approximately 25% of peripheral T cells at baseline, were reduced by 50%, including in both CD4+ and CD8+ subsets, in a dose-dependent manner and in correlation with receptor occupancy.

This effect was maximized on high-PD-1+ Tcon cells, which represented approximately 5% of peripheral T cells, with 90% reduction relative to baseline.

Conversely, total T cells (CD3+), total Tcon cells (CD3+, CD25low) and total regulatory T (Treg) cells (CD3+, CD4+, CD25 bright, CD127-) were unchanged (<5% change from baseline), resulting in a

consistent ratio of PD-1+ Tcon cells to total Treg cells post-treatment in healthy volunteers.

No effect (<5% reduction from baseline) was observed on any of the aforementioned cell types in placebo-dosed subjects.

We plan to conduct a randomized placebo-controlled multi-hundred patient global Phase 2b trial assessing three dose levels of subcutaneously administrated rosnilimab in moderate-to-severe RA for approximately six months on well-established endpoints including ACR 20/50/70 and DAS28.

We expect to initiate this trial in the third quarter of 2023 with top-line interim data anticipated by mid-year 2025.

We also plan to conduct a second global Phase 2 trial, in an indication to be announced, with trial initiation anticipated by the end of 2023.

During the fourth quarter of 2021, we initiated AZURE, a randomized placebo-controlled 45-patient Phase 2 trial of rosnilimab in moderate-to-severe alopecia areata patients.

We conducted an interim review of blinded data in December 2022 which demonstrated robust reductions in peripheral PD-1+ T cells, including PD-1 high T cells reduction of >80%, across blinded pooled rosnilimab patients and placebo patients, which is consistent with observations in the healthy volunteer Phase 1 trial of >90% in rosnilimab treated patients.

The blinded data suggests rosnilimab administration was generally safe and well tolerated.

Interim results suggest that target improvement in severity of alopecia tool (SALT) was not achieved potentially due to an inadequate tested dose level, limited duration of treatment, and/or complexity of disease biology including the hair growth cycle.

Further development in alopecia areata will not be pursued.

The unblinded final results will be available in second half of 2023.

ANB032 is designed to augment BTLA signaling, which is broadly applicable to human inflammatory diseases associated with lymphoid and myeloid immune cell dysregulation.

Genetic studies have demonstrated that BTLA pathway mutations increase human susceptibility to multiple autoimmune diseases and insufficient BTLA signaling can lead to dysregulated T or B cell responses and changes in the function of dendritic cells.

BTLA modulates signaling of HVEM, governing HVEM’s interaction with its natural ligands, including LIGHT.

Polymorphisms in BTLA or molecules in the BTLA pathway such as HVEM are associated with inflammatory diseases, including aberrant T cell activity, B cell activity and dysregulation of downstream humoral immune responses (IgE, IgG secretion).

Similarly, BTLA knockout animals have spontaneous or enhanced severity of inflammatory disease, demonstrating aberrant T cell activity, B cell activity and dysregulation of pathogenic antibody responses upon immunization.

ANB032 is anticipated to down-modulate the activity of T cells, B cells and dendritic cells via several potential mechanisms:

BTLA agonistic activity, stabilization of the interaction of BTLA and HVEM in cis which prevents pro-inflammatory signaling mediated by HVEM ligands such as LIGHT, and abrogation of pro-inflammatory HVEM signaling mediated by BTLA in trans.

No SAEs were reported in subjects receiving multiple doses of rosnilimab or placebo .

Rosnilimab demonstrated a favorable pharmacokinetic (“PK”) profile with an estimated two-week half-life for subcutaneous and IV routes of administration.

Full PD-1 receptor occupancy was observed rapidly and was maintained for at least 30 days.

Potent and sustained reduction was observed in peripheral PD-1+ T cells for >30 days, including >90% reduction of PD-1 high T cells and a >50% reduction of PD-1+ T cells bringing the overall T cell composition to a less activated state, without meaningfully reducing overall T cell numbers.

We also completed a randomized placebo-controlled 45-patient Phase 2 trial assessing a single 400mg monthly dose of rosnilimab over six months in moderate-to-severe alopecia areata patients.

In January 2023, we reported interim results of blinded data which suggested that sufficient improvement in the severity of alopecia tool (SALT) endpoint necessary to justify further development in alopecia was not achieved.

Furthermore, we reported safety and pharmacodynamics data suggesting that rosnilimab was generally well tolerated, with no dose limiting toxicities observed and no SAEs reported.

We are conducting a randomized placebo-controlled 420-patient global Phase 2b trial assessing three dose levels of subcutaneously administrated rosnilimab in moderate-to-severe RA for up to 28 weeks on well-established endpoints including ACR20/50/70 and DAS28-CRP.

We anticipate reporting top-line data on the primary endpoint in the RA trial by mid 2025.

We are also conducting a randomized placebo-controlled 130-patient, global Phase 2 trial assessing two dose levels of subcutaneously administered rosnilimab in moderate-to-severe UC for up to 24 weeks on well-established endpoints including clinical remission on the modified Mayo score (“mMS”), clinical response on the mMS and endoscopic remission.

We anticipate reporting top-line data on the primary endpoint in the UC trial in the first half of 2026.

BTLA, or B and T lymphocyte attenuator, is an inhibitory checkpoint receptor that regulates T cells, B cells, and dendritic cell (“DC”) function.

BTLA is expressed only on immune cells and preferentially on activated immune cells, potentially enabling a broad mechanism of action while avoiding off-target activity.

ANB032 is a non-depleting antibody that binds to BTLA, and is anticipated to down-modulate the activity of T cells, B cells and dendritic cells both in inflamed tissue and the periphery via:

agonism resulting in inhibition of T cell expansion and migration, broad reduction of inflammatory Th1, Th2, Th17 and Th22 cytokines, and modulation of dendritic cells including inhibition of dendritic cell maturation, reduction in costimulatory molecule expression, and enhanced inducement of Tregs.

In in vitro studies, ANB032 demonstrated potent agonism and, in a murine model of GvHD, demonstrated superior disease-modification compared to control antibodies.

We announced positive top-line data from a healthy volunteer Phase 1 trial of ANB032, under a CTN, in April 2022.

A total of 96 subjects were enrolled in the randomized, double-blind, placebo-controlled healthy volunteer Phase 1 trial, where single ascending dose (SAD) cohorts received subcutaneous or IV single doses of ANB032 or placebo, while multiple ascending dose (MAD) cohorts received four weekly subcutaneous doses of ANB032 or placebo.

A total of 96 subjects were enrolled in the randomized, double-blind, placebo-controlled healthy volunteer Phase 1 trial, where SAD cohorts received subcutaneous or IV single doses of ANB032 or placebo, while MAD cohorts received four weekly subcutaneous doses of ANB032 or placebo.

ANB032 was generally well-tolerated and no dose limiting toxicities were observed.

No serious adverse events were reported.

ANB032 demonstrated a favorable pharmacokinetic profile with an estimated two-week half-life for subcutaneous and IV routes of administration.

Full PD-1 receptor occupancy was observed rapidly and was maintained for at least 30 days.

In in vitro studies, ANB032 pharmacodynamic activity demonstrated inhibition of T cell proliferation and reduction in inflammatory cytokine secretion (Th1, Th2, Th17).

While Th2 targeted therapies provide benefit to patients with chronic moderate-to-severe atopic dermatitis (AD), there is compelling evidence that AD is broader than a Th2 driven disease, as Th1, Th17 and other cell types, including dendritic cells, contribute significantly to the pathogenesis.

ANB032 inhibition of inflammatory Th1, Th2 and Th17 activity, and modulation of additional cell types such as B cells and dendritic cells, creates the potential for broader, deeper and more durable responses than more narrowly targeted interventions.

We plan to conduct a randomized placebo-controlled 160 patient Phase 2 trial assessing three dose levels of subcutaneously administrated ANB032 in moderate-to-severe AD for 12 weeks on well-established endpoints including EASI75 and IGA 0/1.

We expect to initiate this clinical trial in the second quarter of 2023 with top-line interim data anticipated by the end of 2024.

No SAEs were reported.

ANB032 demonstrated a favorable PK profile with an estimated two-week half-life for subcutaneous and IV routes of administration.

Full BTLA receptor occupancy was observed rapidly and was maintained for at least 30 days.

While Th2 targeted therapies provide benefit to patients with chronic moderate-to-severe atopic dermatitis (AD), there is compelling evidence that AD is broader than a Th2 driven disease, as Th1, Th17, Th22 and other cell types, including dendritic cells, contribute significantly to the pathogenesis.

ANB032 inhibition of inflammatory Th1, Th2, Th17 and Th22 activity, and modulation of additional cell types such as B cells and dendritic cells, creates the potential for broader, deeper and more durable responses than more narrowly targeted interventions.

We are conducting a randomized placebo-controlled 160 patient global Phase 2b trial assessing three dose levels of subcutaneously administered ANB032 in moderate-to-severe AD for 12 weeks on well-established endpoints including EASI75 and IGA 0/1 measured at week 14.

Patients will then be followed for an additional 24 weeks after the final dose at week 12 to understand longer term safety as well as the potential for prolonged and sustained efficacy.

We anticipate reporting top-line data on the primary endpoint from this trial by the end of 2024.

ANB033 targets CD122, the common beta subunit shared by the IL-15 and IL-2 receptors.

IL-15 signaling mediates the survival and maintenance of tissue resident memory T cells (T RM ).

The presence of long-lived and persistent T RM has been shown to drive tissue-specific immune-mediated inflammation.

T RM are present in the skin in dermatologic diseases, where defined borders of inflammation often recur.

T RM are also observed in other tissue-specific inflammatory disorders including gastroenterology, rheumatology and respiratory.

ANB033 is designed with an affinity to CD122 that inhibits IL-15 signaling, leading to death of pathogenic T RM cells in diseased tissue, with the potential to achieve and maintain remission of inflammation through the elimination of these disease-causing cells.

In addition, ANB033 inhibits IL-2 signaling through the

low affinity IL-2 receptor (comprised of CD122 and the common gamma subunit, CD132) expressed on T cells, while sparing regulatory T cells which express the high affinity IL-2 receptor (comprised of CD122, CD132 and the alpha receptor subunit for IL-2, CD25).

This drives reduction of pathogenic T cell numbers while sparing or potentially enhancing regulatory T cell numbers.

We anticipate submitting an IND for a Phase 1 clinical trial with ANB033 during the first half of 2024.

Imsidolimab inhibits the interleukin-36 receptor (IL-36R) and is being developed for the treatment of GPP.

We completed a Phase 1 clinical trial in healthy volunteers, which was presented at the European Academy of Allergy and Clinical Immunology in 2018, where imsidolimab was well-tolerated, no dose-limiting toxicities were observed, and no serious adverse events were reported.

IL-15 and IL-2 signaling mediate the proliferation and survival of NK cells and certain CD8 T cell subsets.

ANB033 is an antibody designed with an affinity to CD122 that inhibits IL-15 and IL-2 signaling through the low affinity IL-2 receptor (comprised of CD122 and the common gamma subunit, CD132) while sparing IL-2 signaling through the high affinity IL-2 receptor (comprised of CD122, CD132 and the alpha receptor subunit for IL-2, CD25) expressed by regulatory T cells.

This leads to the potential to achieve and maintain remission of inflammation through the reduction of disease-causing NK cells and certain CD8 T cell subsets, while sparing regulatory T cells.

By preventing the consumption of IL-2 by pathogenic cells that express the low affinity IL-2 receptor, circulating levels of IL-2 may increase, potentially enhancing regulatory T cell numbers that express the high affinity

IL-2 receptor in the setting of inflammation.

We anticipate submitting an IND for a Phase 1 clinical trial with ANB033 during the second quarter of 2024.

Blood dendritic cell antigen 2 (“BDCA2”) is a molecule specifically expressed on plasmacytoid dendritic cells (pDCs), a class of immune cells which, while found in relatively small numbers in healthy patients, are enriched in patients with a variety of inflammatory diseases, that is critical to the regulation of toll-like receptor signaling and interferon secretion.

pDCs are a key upstream node in the inflammatory cascade that serve as a bridge between innate and adaptive immunity.

They have been shown to be prolific secretors of type I interferons, which drive activation of a variety of downstream cell types including T cells and monocytes.

Together with their ability to present antigens to the adaptive immune system, this creates a pro-inflammatory environment for the establishment and perpetuation of autoimmune pathology.

BDCA2 has been implicated in the pathophysiology of systemic lupus erythematosus (SLE), where there exists mechanistic clinical proof of concept for pDC modulation.

ANB101 is a BDCA2 modulator antibody that targets pDCs and potently inhibits interferon secretion and modulates antigen presentation for the treatment of autoimmune and inflammatory diseases.

We anticipate submitting an IND for a Phase 1 clinical trial with ANB101 during the second half of 2024.

Imsidolimab is an IgG4 antibody that inhibits the function of the interleukin-36-receptor, or IL-36R, that is being developed for the treatment of GPP.

In July 2020, the FDA granted Orphan Drug Designation for imsidolimab for the treatment of patients with GPP.

We completed an open-label, multi-dose, single-arm Phase 2 clinical trial of imsidolimab in 8 GPP patients, also referred to as the GALLOP clinical trial, where top-line data through week 16 was presented at the European Academy of Dermatology and Venerology (EADV) Congress in October 2021.

We have initiated two Phase 3 trials for imsidolimab for GPP.

The first, called GEMINI-1, will enroll approximately 45 moderate-to-severe GPP patients, each undergoing an active flare at baseline, which will be randomized equally to receive a single dose of 750mg IV imsidolimab, 300mg IV imsidolimab, or placebo.

The primary endpoint of the Phase 3 program is the proportion of patients achieving clear or almost clear skin as determined by a GPPPGA score of zero or 1 at week 4 of GEMINI-1.

Patients completing the GEMINI-1 trial will subsequently be enrolled in GEMINI-2, our second Phase 3 trial for imsidolimab in GPP, where they will receive monthly doses of 200mg subcutaneous imsidolimab or placebo depending upon whether they are responders, partial responders or non-responders to treatment under GEMINI-1.

The objective of GEMINI-2 is to assess the efficacy and safety of imsidolimab after 3 years of monthly dosing.

Top-line data from an interim analysis of GEMINI-1 is anticipated in the fourth quarter of 2023.

We announced in August 2022 that we intend to complete execution of our Phase 3 program in GPP and out-license imsidolimab prior to potential FDA approval.

We initiated two Phase 3 clinical trials for imsidolimab in GPP.

We successfully completed the first randomized placebo-controlled trial, called GEMINI-1, in 45 patients, assessing two, single dose levels of IV-administered imsidolimab.

As of October 2023, of the patients who received a single dose of 750mg IV imsidolimab, 53.3% achieved Generalized Pustular Psoriasis Physician Global Assessment (GPPPGA) 0/1 (clear or almost clear) at Week 4, our primary endpoint, compared to 13.3% of patients on placebo (p=0.0131).

The GPPPGA assessment, representing a stringent and comprehensive characterization of disease severity, required satisfying an overall clinical response score of 0/1 (clear or almost clear) collectively across each GPP disease attribute, including pustulation, erythema and scaling.

Imsidolimab demonstrated favorable safety, tolerability, and immunogenicity with no elevation of infection risk compared to placebo, no serious adverse events, and only 1 of 30 patients treated with imsidolimab generating anti-drug antibodies over the course of the study.

Patients completing the GEMINI-1 trial were eligible to be subsequently enrolled in GEMINI-2, our second Phase 3 trial for imsidolimab in GPP, where they receive monthly doses of 200mg subcutaneous imsidolimab or placebo depending upon whether they are responders, partial responders or non-responders to treatment under GEMINI-1.

Additionally, 66.7% (10/15) of placebo patients exited GEMINI-1 early, crossed-over to GEMINI-2 and were eligible to receive rescue therapy with a single dose of 750mg IV imsidolimab.

The objective of GEMINI-2 is to assess the long-term safety of imsidolimab through 3 years of monthly dosing, as well as assess the efficacy of imsidolimab to reduce the incidence or severity of recurrent flares of GPP.

We intend to out-license imsidolimab in 2024.

Etokimab inhibits IL-33 function and acts upstream of key cell types involved in atopy and the subsequent release of Th2 cytokines.

IL-33 is a pro-inflammatory cytokine that signals through the ST2 receptor, which multiple studies suggest serves as a central mediator of various immune responses leading to Th2-type inflammatory disorders, including asthma, COPD and atopic diseases.

Individuals with asthma symptoms express higher levels of IL-33 than healthy control subjects.

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IL-33 also acts on Th2 effector cells and Innate Lymphoid Cell Type 2 (ILC2), two types of white blood cells that initiate and orchestrate atopic responses.

We have no ongoing clinical trials of etokimab and announced in January 2023 that etokimab is available to out-license.

We have no ongoing clinical trials of etokimab and etokimab is available to out-license.

Collaborative Programs

Multiple Company-discovered antibody programs have been advanced to preclinical and clinical milestones under our collaborations.

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Under the GSK Agreement, a Biologics License Application (“BLA”) for our most advanced partnered program, which is an anti-PD-1 antagonist antibody called Jemperli (dostarlimab), was approved by the FDA in April 2021 for the treatment of advanced or recurrent deficient mismatch repair endometrial cancer (dMMREC).

In February 2023, the FDA granted full approval for this indication (from an accelerated approval).

In February 2023, the FDA granted full

approval for this indication (from an accelerated approval).

In addition, in April 2021 the European Medicines Agency (“EMA”) granted conditional marketing authorization in the European Union (“EU”) for Jemperli for use in women with mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) recurrent or advanced endometrial cancer who have progressed on or following prior treatment with a platinum containing regimen.

A second FDA approval was received in August 2021 for Jemperli in pan-deficient mismatch repair tumors (PdMMRT).

JEMPERLI is currently in Phase 3 trials for various solid tumor indications, including first-line advanced/recurrent endometrial cancer and first-line ovarian cancer.

In addition, under the collaboration, GSK is developing dostarlimab in combination with two other development programs from the GSK Agreement:

cobolimab, an anti-TIM-3 antibody, and GSK40974386, an anti-LAG-3 antibody for multiple solid tumor indications.

GSK is conducting a Phase 3 trial, COSTAR Lung, which is a randomized, open label 3-arm trial comparing cobolimab plus dostarlimab plus docetaxel to dostarlimab plus docetaxel to docetaxel alone in patients with advanced non-small-cell lung cancer (“NSCLC”) who have progressed on prior anti-PD-(L)1 therapy and chemotherapy.

In June 2021, GSK estimated potential peak annual global JEMPERLI sales on a non-risk adjusted basis of £1-£2 billion for currently approved indications and first-line use in endometrial and ovarian cancer only.

In July 2023, the FDA approved Jemperli in combination with chemotherapy for the treatment of adult patients with mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) primary advanced or recurrent endometrial cancer.

In December 2023, the EMA approved, in the EU, Jemperli plus chemotherapy for dMMR/MSI-H primary advanced or recurrent endometrial cancer.

Jemperli is in clinical trials for various solid tumor indications, including a Phase 3 trial in first-line ovarian cancer with top-line results expected in the first half of 2024.

In addition, under the collaboration, GSK is developing dostarlimab in combination with another development program from the GSK Agreement, including cobolimab, an anti-TIM-3 antibody.

Our Product Candidates

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We are a clinical-stage biotechnology company focused on delivering innovative immunology therapeutics.

Our immune cell modulating antibodies, developed internally with our antibody research platform, modulate key nodes governing the body’s regulation of inflammation and autoimmunity.

Dysregulated immune responses may result in abnormal and pathological inflammation in disorders with large and substantially underserved patient populations in the therapeutic areas of dermatology, rheumatology, gastroenterology, respiratory and neurology.

Our immune cell modulating antibodies modulate key nodes governing the body’s regulation of autoimmunity and inflammation.

Dysregulated immune responses may result in abnormal and pathological inflammation in diseases with large and substantially underserved patient populations in the therapeutic areas of dermatology, rheumatology, gastroenterology, respiratory and neurology.

The key elements of our strategy include:

• Enabling broad development of our immune cell modulator portfolio, including our checkpoint agonist programs, rosnilimab and ANB032, in indications including moderate-to-severe RA and AD, respectively.

• Generating in vitro and in vivo translational and clinical data to inform the potential differentiation of our molecules from in-class competitors and, relative to standard of care, treat patient populations most likely to have deeper and/or more durable responses by restoring immune balance.

• Enabling broad development of our immune cell modulator portfolio, including our checkpoint agonist programs, rosnilimab and ANB032, in indications including moderate-to-severe RA, UC and AD.

• Generating in vitro and in vivo translational and clinical data to characterize the differentiation of our molecules from in-class competitors and, relative to standard of care, treat patient populations most likely to have deeper and/or more durable responses by restoring immune balance.

• Facilitating the global commercialization of our checkpoint agonists while retaining rights in key therapeutic areas and/or commercial markets to enable us to become a fully integrated discovery, development and commercial organization.

• Continuing to leverage our research platform to generate potentially best-in-class antibodies against high-value immunological targets.

• Continuing to leverage our research expertise to generate potentially best-in-class antibodies against high-value immunological targets.

• Maximizing return on equity through execution against a multi-year capital and operating plan, including the potential for future royalty revenues from our GSK immuno-oncology collaboration and, where actionable, monetizing our legacy cytokine antagonist programs and enabling further external development and, potentially, commercialization.

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Antibodies are structurally distinct Y-shaped proteins formed through the combination of two long proteins, called heavy chains, and two short proteins, called light chains.

heavy and light chain pair forms a binding site where the antibody specifically binds its target, otherwise known as an antigen, at the Fab domain of the antibody molecule.

Each heavy and light chain pair forms a binding site where the antibody specifically binds its target, otherwise known as an antigen, at the Fab domain of the antibody molecule.

The specificity of each antibody to a target, and the potency of its binding strength to that target are defined by the amino acid sequences of heavy and light chains in the Fab domain of the antibody molecule.

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Hence, antibodies tend to be dosed at low amounts (less than 1 gram quantities per course of therapy).

Limitations of Competing Antibody Technologies

Despite the promise of antibodies as a therapeutic modality, historically it has been difficult and time consuming to generate therapeutic-grade antibodies utilizing competing antibody discovery technologies.

Such technologies have relied primarily on mouse immunization methodologies (such as wild-type or engineered mice), microbial antibody display libraries (such as phage or yeast cell display) or human B cell screening to generate antibodies against therapeutic targets of interest.

We believe the key limitations of these competitive approaches include insufficient diversity, lack of functional activity selection, and low potency.

Antibody discovery technologies are often not utilized in combination, or iteratively in combination, or utilized in the appropriate immunological setting that would be conducive to co-discovery of appropriate Fab and Fc domains that work together to accomplish more challenging therapeutic mechanisms of action, such as immune cell modulation.

Our Antibody Research Platform

Our innovative antibody research platform is designed to discover and optimize therapeutic antibodies that are tailored to modulate immune function, whether they may be antagonists or immune cell modulators.

Discovery and optimization occurs first on the Fab domain of the antibody where we often utilize a technology that replicates the natural process of somatic hyper mutation (“SHM”) employed by the human immune system through the expression of a key enzyme called activation-induced cytidine deaminase, (“AID”).

SHM is a critical, endogenous process that generates the essential antibody diversity required to develop a natural immune response to pathogens, expanding the limited diversity encoded within human genomes to billions of antibody specificities.

By coupling in vitro SHM with our mammalian cell system that simultaneously displays and secretes

antibodies, we believe SHM rapidly evolves in an iterative fashion the binding potency and function of antibodies to levels that we believe will be required for therapeutic use with high potency functional activity while simultaneously mitigating potential manufacturing liabilities.

In addition to optimizing the Fab domain of antibodies for therapeutic purposes using in vitro SHM, we also optimize the Fc domain of the antibody, when needed, to tailor it for specific activity.

Appropriate Fc domains are utilized to reduce Fc receptor interactions or to optimize Fc receptor interactions, in combination with the Fab domain of the antibody, to specifically modulate immune cell function, engage effector function that kills specific targeted immune cells, or leverage a combination of both activities.

Our approach to antibody design focuses on discovering and optimizing therapeutic antibodies tailored to modulate immune function.

We use a variety of technologies to optimize the Fab domain of an antibody in ways that we believe both create a therapeutic antibody with highly potent functional activity and mitigate potential manufacturing liabilities.

We also optimize the Fc domain of the antibody, when needed, to tailor it for specific activity such as reducing Fc receptor interactions or optimizing Fc receptor interactions, in combination with the Fab domain of the antibody, to specifically modulate immune cell function, engage effector function that kills specific targeted immune cells, or leverage a combination of both activities.

We further optimize the overall antibody through humanization and removal of liabilities that could potentially affect the structure, stability, pharmacology, manufacturability or immunogenicity of the antibody.

Optimized antibodies are tested in an extensive suite of immune cell assays, using engineered cell lines, and more relevantly, primary human immune cells from healthy and diseased individuals that we believe most accurately recapitulates the conditions in which the antibody will need to have optimal activity in patients.

We believe that by combining the in vitro SHM discovery platform with an appropriate Fc domain, in combination with a suite of primary immune cell assays, and finally in vivo functional assessment, we effectively tailor antibody discovery to achieve a unique therapeutic benefit.

Optimized antibodies are tested in an extensive suite of immune cell assays, using engineered cell lines, and more relevantly, primary human immune cells from healthy and diseased individuals that we believe most accurately recapitulate the conditions in which the antibody will need to have optimal activity in patients.

We believe that our approach to antibody design allows us to effectively tailor antibody discovery to achieve a unique therapeutic benefit.

Collaborations

GlaxoSmithKline

In March 2014, we entered into a Collaboration and Exclusive License Agreement with GSK (the “GSK Agreement”) for the development and commercialization of therapeutic monospecific and bispecific antibodies that antagonize PD-1, TIM-3, LAG-3 and/or a fourth undisclosed checkpoint receptor.

We received $17.0 million in upfront fees from GSK in March 2014, and in November 2014, we amended the agreement with GSK to include the development and commercialization of bispecific antibodies to another undisclosed target, for an additional upfront fee of $2.0 million.

Both upfront fees were recognized over the same period that our research and development services for which we were reimbursed were performed, which was extended through December 31, 2016 by amendment of the GSK Agreement in February 2016.

For each of the targets under the GSK agreement, we are eligible to receive up to $273.0 million in milestone payments, which are comprised of $18.0 million for preclinical and clinical development milestone payments, $90.0 million upon certain regulatory events and $165.0 million upon worldwide commercial sales thresholds.

In addition, GSK is obligated to pay us tiered royalties, ranging from 4% to 8%, for each product developed under the agreement, except in the case of JEMPERLI where the royalties payable will be 8% to 25% as described below, on annualized net sales of each antibody commercialized from the collaboration.

On October 23, 2020, we amended the GSK Agreement (the “2020 Amendment”).

Under the 2020 Amendment, we were granted increased royalties upon sales of JEMPERLI (dostarlimab), an anti-PD-1 antagonist antibody under development by GSK for multiple oncological disorders, equal to 8% of Net Sales (as defined in the GSK Agreement) below $1.0 billion and from 12% up to 25% of Net Sales above $1.0 billion.

The 2020 Amendment also provided for a one-time non-refundable cash payment of $60.0 million that we received in the fourth quarter of 2020.

The $1.1 billion in cash milestone payments due under the GSK Agreement remain unchanged.

Additionally, under the terms of the 2020 Amendment, GSK has agreed to certain diligence commitments with respect to the future development of JEMPERLI, and the parties have agreed to review such commitments under regular joint review committee meetings going forward.

In October 2021, we entered into the JEMPERLI Royalty Monetization Agreement (the “JEMPERLI Royalty Monetization Agreement”) with Sagard.

In March 2014, we entered into a Collaboration and Exclusive License Agreement with GSK (the “GSK Agreement”) with TESARO, Inc.

(“Tesaro”), an oncology-focused biopharmaceutical company now a part of GlaxoSmithKline (Tesaro and GlaxoSmithKline are hereinafter referred to, collectively, as “GSK”).

Under the terms of the GSK Agreement, as amended, we agreed to perform certain discovery and early preclinical development of therapeutic antibodies with the goal of generating immunotherapy antibodies for subsequent preclinical, clinical, regulatory, and commercial development to be performed by GSK.

Under the terms of the GSK Agreement, GSK agreed to provide funding to us for research and development services related to antibody discovery programs for three specific targets.

Currently, under the GSK Agreement, GSK is developing Jemperli (dostarlimab), an anti-PD-1 antagonist antibody, as a monotherapy for various solid tumor indications.

In addition, GSK is developing dostarlimab in combination with additional therapies under the collaboration, including with another development program from the GSK Agreement:

cobolimab, an anti-TIM-3 antibody, in 2L NSCLC.

In October 2023, Amendment No.

5 to the GSK Agreement was agreed by both parties to terminate the anti-LAG-3 antagonist antibody development program under the GSK Agreement.

In accordance with the GSK Agreement and this amendment, we have regained full global rights to the anti-LAG-3 antagonist antibody development program.

For each remaining development program under the GSK Agreement, we are eligible to receive milestone payments if certain preclinical and clinical trial events are achieved by GSK, if certain U.S.

and European regulatory submissions and approvals in multiple indications are achieved, and upon the achievement of specified levels of annual worldwide net sales.

We will also be eligible to receive tiered 4-8% royalties related to worldwide net sales of products developed under the collaboration.

On October 23, 2020, Amendment No.

3 to the GSK Agreement (the “Amendment”) was agreed to by both parties to permit GSK to conduct development and commercialization in combination with any third-party molecules of Zejula, an oral, once-daily poly (ADP-ribose) polymerase (PARP) inhibitor.

Under the Amendment, we were granted increased royalties upon sales of Jemperli , equal to 8% of Net Sales (as defined in the GSK Agreement) below $1.0 billion and from 12% up to 25% of Net Sales above $1.0 billion.

In October 2021, we signed a royalty monetization agreement (the “ Jemperli Royalty Monetization Agreement”) with Sagard Healthcare Royalty Partners, LP (“Sagard”).

Under the terms of the Jemperli Royalty Monetization Agreement, we received $250.0 million, upon closing in December 2021, in exchange for royalties payable to us under the GSK collaboration on annual global net sales of Jemperli below $1.0 billion, as well as certain milestone payments, starting in October 2021.

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For more information see Note 5 — Sale of Future Royalties in the accompanying notes to the consolidated financial statements.

This GSK Agreement, as amended, expires when no further payments are due to us, unless earlier terminated.

The GSK Agreement, as amended, expires when no further payments are due to us, unless earlier terminated.

Either party may terminate the GSK Agreement, as amended, in the event of an uncured material breach by the other party.

GSK may terminate the GSK Agreement, as amended, at any time upon 90 days’ prior written notice to us.

Under the GSK Agreement, a Biologics License Application (“BLA”) for our most advanced partnered program, which is an anti-PD-1 antagonist antibody called JEMPERLI (dostarlimab), was approved by the FDA in April 2021 for the treatment of advanced or recurrent deficient mismatch repair endometrial cancer (dMMREC).

In February 2023, the FDA granted full approval for this indication (from an accelerated approval).

In addition, in April 2021 the European Medicines Agency (“EMA”) granted conditional marketing authorization in the European Union (“EU”) for JEMPERLI for use in women with mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) recurrent or advanced endometrial cancer who have progressed on or following prior treatment with a platinum containing regimen.

A second FDA approval was received in August 2021 for JEMPERLI in pan-deficient mismatch repair tumors (PdMMRT).

JEMPERLI is currently in Phase 3 trials for various solid tumor indications, including first-line advanced/recurrent endometrial cancer and first-line ovarian cancer.

In addition, under the collaboration, GSK is developing dostarlimab in combination with two other development programs from the GSK Agreement:

cobolimab, an anti-TIM-3 antibody, and GSK40974386, an anti-LAG-3 antibody for multiple solid tumor indications.

GSK is conducting a Phase 3 trial, COSTAR Lung, which is a randomized, open label 3-arm trial comparing cobolimab plus dostarlimab plus docetaxel to dostarlimab plus docetaxel to docetaxel alone in patients with advanced NSCLC who have progressed on prior anti-PD-(L)1 therapy and chemotherapy.

Bristol-Myers Squibb

In December 2011, we entered into a license and collaboration agreement (the “BMS Agreement”) with Celgene, now a part of Bristol-Myers Squibb (Celgene and Bristol-Myers Squibb are hereinafter referred to, collectively, as “BMS”), to develop therapeutic antibodies against multiple targets.

We granted BMS the option to obtain worldwide commercial rights to antibodies generated against each of the targets under the agreement, which option was triggered on a target-by-target basis by our delivery of antibodies meeting certain pre-specified parameters pertaining to each target under the agreement.

The BMS Agreement provided for an upfront payment of $6.0 million from BMS, which we received in 2011, and recognized through 2014, milestone payments of up to $53.0 million per target, low single-digit royalties on net sales of antibodies against each target, and reimbursement of specified research and development costs.

The BMS Agreement continues until our royalty rights on any BMS product resulting from the collaboration expire, which period will last at least ten years after any such product first goes to market.

Either we or BMS may terminate the BMS Agreement in the event of an uncured material breach by the other party.

In-Licensing Agreements License Agreement with UKRI

In 2006, we entered into an exclusive worldwide license agreement with the Medical Research Council, which has subsequently been acquired by United Kingdom Research and Innovation (“UKRI”), to obtain rights to multiple patents and patent applications relating to fundamental discoveries with respect to SHM and AID.

We since amended this license agreement to include additional subject matter and reflect the change in ownership.

Under the terms of the agreement (the “UKRI Agreement”), we obtained an exclusive, worldwide, sub-licensable license under specified patent rights to manufacture, use, sell and commercialize products and methods covered by such patents for all fields of use.

We are responsible for prosecution of the licensed patents and the development of therapeutic products covered by the intellectual property.

We are responsible for paying UKRI an annual fee of $55,000.

Additionally, for each product developed and commercialized under the UKRI Agreement, we are obligated to pay UKRI up to an additional $175,000 upon the achievement of specified development milestone events and up to an additional $275,000 upon the achievement of specified regulatory milestone events.

In addition, we owe UKRI royalties at 0.25% of annual net sales for worldwide sales on a product-by-product at or below $750.0 million and 1% of annual net sales of products worldwide above $750.0 million, payable on a country-by-country basis until the expiration of the last licensed patent covering such product in such country.

Under this license agreement, we have rights to 10 patents worldwide as of December 31, 2022.

Unless earlier terminated, the UKRI Agreement will expire upon expiration of all royalty payment obligations under the UKRI Agreement.

Either party may terminate the UKRI Agreement in the event of an uncured material breach by the other party or upon the occurrence of specified bankruptcy events for the other party.

We may terminate the UKRI Agreement upon 60 days’ notice to UKRI.

License Agreement with Millipore

In May 2009, we signed a non-exclusive research and commercial license agreement with Millipore Corporation, or Millipore, to obtain a non-exclusive license to patents and patent applications directed to the ubiquitous chromatin opening elements technology for the expression of proteins, particularly antibodies, generated by us, which license may be sublicensed to our contractors and partners.

Under the terms of the agreement, (the “Millipore Agreement”), we are obligated to pay Millipore $87,500 in annual license fees, adjusted annually for inflation using the Consumer Price Index.

Additionally, for each product developed and commercialized under the Millipore Agreement, we are obligated to pay Millipore up to an additional $750,000 upon the achievement of specified development milestone events and up to an additional $4.4 million upon the achievement of specified commercial milestone events.

We do not owe Millipore any royalties on net sales of products commercialized under the Millipore Agreement.

Unless affirmatively terminated by one of the parties, the Millipore Agreement will continue in effect.

Either party may terminate the Millipore Agreement in the event of an uncured material breach by the other party.

We may terminate the Millipore Agreement upon 90 days’ notice to Millipore.

Intellectual Property

Our intellectual property is critical to our business and we strive to protect it, including by obtaining and maintaining patent protection in the United States and internationally for our technology platform, product candidates, novel biological discoveries, epitopes, new therapeutic approaches and potential indications, and other inventions that are important to our business.

In total, our patent portfolio, including patents to our technology platform licensed from UKRI, as well as patents co-owned with GSK consisted of approximately 82 issued patents and 90 pending patent applications as of December 31, 2022.

Our intellectual property is critical to our business and we strive to protect it, including by obtaining and maintaining patent protection in the United States and internationally for product candidates, novel biological discoveries, epitopes, new therapeutic approaches and potential indications, and other inventions that are important to our business.

In total, our patent portfolio, including patents co-owned with GSK, patents licensed from Centessa Pharmaceuticals (UK) Ltd., and patents to

certain antibody discovery technology consisted of approximately 93 issued patents and 103 pending patent applications as of December 31, 2023.

For our product candidates, generally we initially pursue patent protection covering compositions of matter including antibody sequences, methods of use, and methods of production.

Throughout the development of our product candidates, we seek to identify additional means of obtaining patent protection that would potentially enhance commercial success.

The patent portfolios for our internal programs and platform technology are outlined below:

The patent portfolios for our internal programs are outlined below:

As of December 31, 2023, we owned 16 patent applications in various countries directed to the antibody sequence of rosnilimab and its variants, methods of use and related matters.

We intend to prosecute our pending applications and pursue patent issuance and protection in key commercial markets where significant product sales may occur.

Patents that may issue from our pending applications could provide protection until June 2040.

As of December 31, 2022, we owned one international (PCT) patent application and one U.S.

provisional patent application directed to the antibody sequence of ANB032 and its variants, methods of use and related matters.

We intend to prosecute the pending international patent application and file additional patent applications claiming priority to the U.S.

provisional patent application, and pursue patent issuance and protection in key commercial markets where significant product sales may occur.

Patents that may issue from our pending applications, or other patent applications claiming priority thereto, could provide protection until April 2043.

As of December 31, 2022, we owned one pending U.S.

We intend to prosecute our pending applications, and/or other patent applications claiming priority thereto, and pursue patent issuance and protection in key commercial markets where significant product sales may occur.

Patents that may issue from or claim priority to our pending applications could provide protection for aspects of this product candidate until June 2040.

As of December 31, 2023, we owned 16 patent applications in various countries, one international (PCT) patent application and one U.S.

provisional patent application directed to the antibody sequence of ANB032 and its variants, methods of use and related matters.

We intend to file additional patent applications claiming priority to the U.S.

provisional patent application, and pursue patent issuance, in key commercial markets where significant product sales may occur.

Patents that may issue claiming priority to our provisional patent application could provide protection until November 2043.

We intend to prosecute the pending patent applications, and/or other patent applications claiming priority thereto, and pursue patent issuance and protection in key commercial markets where significant product sales may occur.

Patents that may issue from or claim priority to our pending applications could provide protection for aspects of this product candidate until May 2044.

As of December 31, 2023, we owned one international (PCT) patent application directed to the antibody sequence of ANB033 and its variants, methods of use and related matters.

We intend to prosecute the pending international (PCT) patent application, file additional patent applications claiming priority to the international (PCT) patent application, and pursue patent issuance, in key commercial markets where significant product sales may occur.

Patents that may issue claiming priority to our international (PCT) patent application could provide protection for aspects of this product candidate until November 2043.

As of December 31, 2023, we owned rights to 13 patent applications in various countries directed to the antibody sequence of ANB101/102 and their variants, methods of use and related matters.

We intend to prosecute the pending applications, and/or other patent applications claiming priority thereto, and pursue patent issuance and protection in key commercial markets where significant product sales may occur.

Patents that may issue from or claim priority to the pending applications could provide protection for aspects of these product candidates until August 2040.

As of December 31, 2023, we owned 51 patents and patent applications in various countries directed to the antibody sequence of imsidolimab and its variants, methods of use and related matters.

We intend to prosecute our pending applications and pursue patent issuance and protection in key commercial markets where significant product sales may occur.

Patents that have issued or may issue from our pending applications could provide protection until May 2042.

Patents that have issued, or that may issue from or claim priority to our pending applications could provide protection for aspects of this product candidate until May 2042.

As of December 31, 2022, we owned 18 patents and patent applications in various countries directed to the antibody sequence of etokimab and its variants, methods of use and related matters.

We intend to prosecute our pending applications and pursue patent issuance and protection in key commercial markets where significant product sales may occur.

Patents that have issued or may issue from our pending applications could provide protection until January 2035.

Patents that have issued, or that may issue from or claim priority to our pending applications could provide protection for aspects of this product candidate until January 2035.

Dostarlimab (GSK4057190)

As of December 31, 2023, we owned or co-owned 24 patents and patent applications in various countries directed to the antibody sequence of GSK4057190 (dostarlimab), an anti-PD-1 antagonist, and its variants, methods of use and related matters.

We intend to prosecute our pending applications and pursue patent issuance and protection in key commercial markets where significant product sales may occur.

Patents that have issued or may issue from our pending applications could provide protection until June 2038.

We intend to prosecute our pending applications, and/or other patent applications claiming priority thereto, and pursue patent

issuance and protection in key commercial markets where significant product sales may occur.

Patents that have issued, or that may issue from or claim priority to our pending applications, could provide protection for aspects of this product until June 2038.

Cobolimab (GSK4069889)

As of December 31, 2023, we owned or co-owned 24 patents and patent applications in various countries directed to the antibody sequence of GSK4069889 (cobolimab), an anti-TIM-3 antagonist, and its variants, methods of use and related matters.

We intend to prosecute our pending applications and pursue patent issuance and protection in key commercial markets where significant product sales may occur.

Patents that have issued or may issue from our pending applications could provide protection until November 2037.

As of December 31, 2022, we owned or co-owned 37 patents and patent applications in various countries directed to the antibody sequence of GSK4074386, an anti-LAG-3 antagonist, and its variants, methods of use and related matters.

We intend to prosecute our pending applications and pursue patent issuance and protection in key commercial markets where significant product sales may occur.

Patents that have issued or may issue from our pending applications could provide protection until April 2038.

Platform Technology

Our platform technology is covered by U.S.

and foreign issued patents, emanating from our in-licensed portfolio and wholly-owned portfolio, in various jurisdictions.

Our portfolio includes patents directed to platform technology related inventions associated with antibody library design, antibody humanization, mammalian cell display and secretion, and other technical attributes relating to the discovery, maturation and optimization of antibodies using our technology platform.

Patents relating to our platform technology that have been issued to date provide protection through May 2033.

Patents that have issued, or that may issue from or claim priority to our pending applications, could provide protection for aspects of this product candidate until November 2037.

Other Intellectual Property Matters

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In addition, the coverage claimed in a patent application can be significantly reduced before the patent is issued, and its scope can be reinterpreted after issuance.

Consequently, we may not obtain or maintain adequate patent protection for any of our product candidates or for our technology platform.

Consequently, we may not obtain or maintain adequate patent protection for any of our product candidates.

We cannot predict whether the patent applications we are currently pursuing will issue as patents in any particular jurisdiction or whether the claims of any issued patents will provide sufficient proprietary protection from competitors.

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Patent term extension cannot extend the remaining term of a patent beyond a total of 14 years from the date of product approval and only one patent applicable to an approved drug may be extended.

Similar provisions are available in Europe and

other foreign jurisdictions to extend the term of a patent that covers an approved drug.

Similar provisions are available in Europe and other foreign jurisdictions to extend the term of a patent that covers an approved drug.

In the future, if and when our products receive FDA approval, we expect to apply for patent term extensions on patents covering those products.

We plan to seek patent term extensions to any of our issued patents in any jurisdiction where these are available, however there is no guarantee that the applicable authorities, including the FDA in the United States, will agree with our assessment of whether such extensions should be granted, and if granted, the length of such extensions.

We also rely on trade secrets relating to our technology platform and product candidates and seek to protect and maintain the confidentiality of proprietary information to protect aspects of our business that are not amenable to, or that we do not consider appropriate for, patent protection.

We also rely on trade secrets relating to our research and development and product candidates and seek to protect and maintain the confidentiality of proprietary information to protect aspects of our business that are not amenable to, or that we do not consider appropriate for, patent protection.

Although we take steps to protect our proprietary information and trade secrets, including through contractual means with our employees and consultants, third parties may independently develop substantially equivalent proprietary information and techniques or otherwise gain access to our trade secrets or disclose our technology.

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Manufacturing

We must manufacture drug product for clinical trial use in compliance with current good manufacturing practices (“cGMP”).

The cGMP regulations include requirements relating to organization of personnel, buildings and facilities, equipment, control of components and drug product containers and closures, production and process controls, packaging and labeling controls, holding and distribution, laboratory controls, records and reports, and returned or salvaged products.

The manufacturing facilities for our product candidates must meet cGMP requirements and FDA satisfaction before any product is approved and we can manufacture commercial products.

Our third-party manufacturers will also be subject to periodic inspections of facilities by the FDA and other authorities, including procedures and operations used in the testing and manufacture of our products to assess our compliance with applicable regulations.

We must manufacture our product candidates for clinical trial use in compliance with current good manufacturing practices (“cGMP”).

The cGMP regulations include requirements relating to organization of personnel, buildings and facilities, equipment, control of materials, components and drug product containers and closures, production and process controls, packaging and labeling controls, holding and distribution, laboratory controls, records and reports, and returned or salvaged

The manufacturing facilities for our product candidates must meet cGMP requirements and global regulatory requirements before any product is approved and we can manufacture commercial products.

Our third-party manufacturers will be subject to periodic regulatory inspections of facilities by the FDA and other authorities, including procedures and operations used in the testing and manufacture of our products to assess compliance with applicable regulations.

Our internal manufacturing capabilities include non-cGMP antibody and reagent production using small scale quantities for characterization and in vitro and in vivo preclinical assessment of product candidates.

We do not have and we do not currently plan to acquire or develop the facilities or capabilities to manufacture cGMP drug substance or filled drug product for use in human clinical trials.

We rely on third-party manufacturers to generate cGMP-grade cell lines and will rely on them to produce cGMP drug product required for our clinical trials, and we expect to continue to rely on third parties to manufacture clinical trial drug supplies for the foreseeable future.

We also contract with additional third parties for the filling, labeling, packaging, storage and distribution of investigational drug products.

We do not have and we do not currently plan to acquire or develop the facilities or capabilities to manufacture our product candidates for use in human clinical trials.

We rely on third-party manufacturers to generate cGMP compliant cell lines and will rely on them to produce cGMP drug substance and drug product required for our clinical trials, and we expect to continue to rely on third parties to manufacture clinical trial drug supplies for the foreseeable future.

We also contract with additional third parties for the testing, labeling, packaging, storage and distribution of investigational drug products.

We have personnel with significant technical, manufacturing, analytical, quality, including cGMP, and project management experience to oversee our third-party manufacturers and to manage manufacturing and quality data and information for regulatory compliance purposes.

While our contract manufacturers have not yet produced commercially-approved cGMP batches of our product candidates, they have previously manufactured products for other companies in compliance with cGMP and have been previously inspected by regulatory authorities for compliance with cGMP standards.

Similarly, our personnel have had experience with cGMP at previous positions.

Failure to comply with statutory and regulatory requirements subjects a manufacturer to possible legal or regulatory action, including warning letters, the seizure or recall of products, injunctions, consent decrees placing significant restrictions on or suspending manufacturing operations and civil and criminal penalties.

These actions could have a material impact on the availability of our products.

Contract manufacturers often encounter difficulties involving production yields, quality control and quality assurance, as well as shortages of qualified personnel.

Third-party manufacturers often encounter difficulties involving production yields, quality control and quality assurance, as well as shortages of qualified personnel.

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

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

For our anti-PD-1 agonist antibody program, our competitors include other anti-PD-1 agonist antibodies peresolimab (Eli Lilly) in Phase 2b development for the treatment of rheumatoid arthritis, JNJ-67484703 (Janssen) in Phase 2 development, a PD-1 agonist antibody (Boehringer Ingelheim) in Phase 1 development, PT627 and PT001 (Pandion Therapeutics, which has been acquired by Merck) in preclinical development, and MB151 (MiroBio, which has been acquired by Gilead) in preclinical development.

Our competitors in moderate-to-severe rheumatoid arthritis include monoclonal antibodies targeting anti-TNF (Humira;

For our PD-1 agonist antibody program, our competitors include other PD-1 agonist antibodies peresolimab (Eli Lilly) in Phase 2b development for the treatment of rheumatoid arthritis, JNJ-67484703 (Janssen) in Phase 2 development for the treatment of atopic dermatitis, a PD-1 agonist antibody (Boehringer Ingelheim) in Phase 1 development, and GS-0151 (Gilead) in preclinical development.

Our commercial-stage competitors in moderate-to-severe rheumatoid arthritis include monoclonal antibodies targeting anti-TNF (Humira;

Abbvie), IL-6 (Actemra;

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Eli Lilly, and Xeljanz;

For our anti-BTLA agonist antibody program, our competitors include other anti-BTLA agonist antibodies LY3361237 (Eli Lilly) in Phase 2 development, which has demonstrated efficacy in treatment of systemic lupus erythematosus as measured by the cutaneous lupus erythematosus disease area and severity index (CLASI), and MB272 (MiroBio, in Phase 1 development which has been acquired by Gilead).

Our competitors in moderate-to-severe atopic dermatitis include topical and oral corticosteroids, calcineurin inhibitors (Protopic;

Commercial-stage competitors in moderate-to-severe ulcerative colitis include monoclonal antibodies targeting anti-TNF (Humira;

Abbvie and Remicade;

Johnson & Johnson), anti-α4β7 (Entyvio;

Takeda), anti-IL-23 (Stelara;

Johnson & Johnson and Omvoh;

Eli Lilly) and S1P inhibitors (Zeposia;

Bristol Myers Squibb and Velsipity;

Pfizer) and janus kinase inhibitors (Rinvoq;

AbbVie, and Xeljanz;

Pfizer) as well as monoclonal antibodies targeting anti-TL1A (PRA023;

Merck, RVT-3101;

Roche and TEV’574;

Teva/Sanofi) in Phase 2 and 3 development.

For our BTLA agonist antibody program, our competitors include another BTLA agonist antibody, GS-0272 (Gilead) in Phase 1b development for SLE and rheumatoid arthritis.

Commercial-stage competitors in moderate-to-severe atopic dermatitis include topical and oral corticosteroids, calcineurin inhibitors (Protopic;

LEO Pharma and Elidel;

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Regeneron/Sanofi), IL-13 (Adbry;

LEO Pharma and lebrikizumab;

Eli Lilly), IL-31 (nemolizumab;

Galderma), OX-40L (amlitelimab;

Sanofi), and janus kinase inhibitors (Rinvoq;

LEO Pharma and Ebglyss;

Lilly), IL-31 (nemolizumab;

Galderma) and janus kinase inhibitors (Rinvoq;

AbbVie and abrocitinib;

For our anti-CD122 antagonist antibody program, our competitors include one other anti-CD122 antagonist antibody, auremolimab (Villaris Therapeutics, which has been acquired by Incyte), currently in preclinical development, and an anti-IL-15 monoclonal antibody, AMG 714 (Amgen), currently in Phase 2 development for the treatment of vitiligo.

For imsidolimab in the treatment of GPP, our competitors include one other anti-IL-36 receptor antibody called SPEVIGO or spesolimab (Boehringer Ingelheim), recently approved for GPP flares in adults.

Pfizer) as well as monoclonal antibodies targeting OX-40/OX40L (rocatinlimab;

Amgen and amlitelimab;

Sanofi) in Phase 3 development.

For our anti-CD122 antagonist antibody program, our clinical competitors include other anti-CD122 antagonist antibodies, auremolimab (Incyte), in Phase 1 development for vitiligo and FB-102 (Forte Bioscience) in preclinical development, and three anti-IL-15 monoclonal antibodies, AMG 714 (Amgen), currently in Phase 2 development for the treatment of vitiligo, CALY-002 (Calypso, which Novartis has agreed to acquire), currently in Phase 1b development for the treatment of celiac disease and eosinophilic esophagitis, and TEV-‘408 (Teva), currently in Phase 1b development for the treatment of celiac disease.

For our anti-BDCA2 program, our competitors include one other anti-BDCA2 antibody, litifilimab (Biogen) in Phase 3 development for SLE and CLE, and one clinical-stage anti-ILT7 antibodies that target plasmacytoid dendritic cells for depletion, daxdilimab (Amgen) in Phase 2 development for alopecia areata, dermatomyositis or anti-synthetase inflammatory myositis, and discoid lupus erythematosus.

For imsidolimab in the treatment of GPP, our competitors include one other anti-IL-36 receptor antibody called SPEVIGO or spesolimab (Boehringer Ingelheim), approved for GPP flares in adults.

Government Regulation and Product Approval

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The Federal Food, Drug, and Cosmetic Act (“FDC Act”), and other federal and state statutes and regulations, govern, among other things, the research, development, testing, manufacture, storage, recordkeeping, approval, labeling, promotion and marketing, distribution, post-approval monitoring and reporting, sampling, and import and export of pharmaceutical products.

Biological products used for the prevention, treatment, or cure of a disease or condition of a human being are subject to regulation under the FDC Act,

except the section of the FDC Act which governs the approval of new drug applications (“NDAs”).

Biological products used for the prevention, treatment, or cure of a disease or condition of a human being are subject to regulation under the FDC Act, except the section of the FDC Act which governs the approval of new drug applications (“NDAs”).

Biological products are approved for marketing under provisions of the Public Health Service Act (“PHSA”), via a BLA.

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(i) in compliance with federal regulations;

(ii) in compliance with good clinical practices (“GCPs”), an international standard meant to protect the rights and health of patients and to define the roles of clinical trial sponsors, administrators, and monitors;

(ii) in compliance with good

clinical practices (“GCPs”), an international standard meant to protect the rights and health of patients and to define the roles of clinical trial sponsors, administrators, and monitors;

as well as (iii) under protocols detailing the objectives of the trial, the parameters to be used in monitoring safety, and the effectiveness criteria to be evaluated.

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Most such applications for standard review biologic products are reviewed within 10 months of the date the BLA is filed with the FDA;

most applications for priority review biologics are reviewed within

six months of the date the BLA is filed with the FDA.

most applications for priority review biologics are reviewed within six months of the date the BLA is filed with the FDA.

Priority review can be applied to a biologic that the FDA determines has the potential to treat a serious or life-threatening condition and, if approved, would be a significant improvement in safety or effectiveness compared to available therapies.

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REMS can include medication guides, communication plans for health care 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 patient registries.

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 patient registries.

The requirement for a REMS can materially affect the potential market and profitability of the product.

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Unless otherwise required by regulation, the PREA does not apply to any biological product for an indication for which Orphan Drug Designation has been granted.

The Best Pharmaceuticals for Children Act (“BPCA”), provides sponsors of NDAs with an additional six-month period of market exclusivity for all unexpired patent or non-patent exclusivity on all forms of the drug containing the active moiety if the sponsor submits results of pediatric studies specifically requested by the FDA under BPCA within required timeframes.

The Best Pharmaceuticals for Children Act (“BPCA”) provides sponsors of NDAs with an additional six-month period of market exclusivity for all unexpired patent or non-patent exclusivity on all forms of the drug containing the active moiety if

the sponsor submits results of pediatric studies specifically requested by the FDA under BPCA within required timeframes.

The BPCA provides sponsors of BLAs an additional six-month extension for all unexpired non-patent market exclusivity on all forms of the biological containing the active moiety pursuant to the BPCA if the conditions under the BPCA are met.

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The time can be shortened if FDA determines that the applicant did not pursue approval with due diligence.

The total patent term after the extension may not exceed 14 years.

The total patent term after the extension may not exceed 14 years from the date of marketing approval.

For patents that might expire during the application phase, the patent owner may request an interim patent extension.

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must comply with applicable provisions of the Drug Supply Chain Security Act and provide and receive product tracing information, maintain appropriate licenses, ensure they only work with other properly licensed entities and have procedures in place to identify and properly handle suspect and illegitimate products.

FDA regulation of companion diagnostics

If use of an in vitro diagnostic is essential for safe and effective use of a drug or biologic product, then the FDA generally will require approval or clearance of the diagnostic, known as a companion diagnostic, at the same time that the FDA approves the therapeutic product.

The review of an in vitro companion diagnostic in conjunction with the review of a biologic involves coordination of review by the FDA’s Center for Biologics Evaluation and Research and by the FDA’s Center for Devices and Radiological Health.

Pursuing FDA approval of an in vitro companion diagnostic would require us to obtain a premarket approval (“PMA”).

The PMA process, including the gathering of clinical and preclinical data and the submission to and review by the FDA, can take several years or longer.

It involves a rigorous premarket review during which the applicant must prepare and provide the FDA with reasonable assurance of the device’s safety and effectiveness and information about the device and its components regarding, among other things, device design, manufacturing and labeling.

PMA applications are

subject to an application fee, which exceeds $250,000 for most PMAs.

In addition, PMAs for certain devices must generally include the results from extensive preclinical and adequate and well-controlled clinical trials to establish the safety and effectiveness of the device for each indication for which FDA approval is sought.

In particular, for a diagnostic, the applicant must demonstrate that the diagnostic produces reproducible results when the same sample is tested multiple times by multiple users at multiple laboratories.

As part of the PMA review, the FDA will typically inspect the manufacturer’s facilities for compliance with the Quality System Regulation (“QSR”), which imposes elaborate testing, control, documentation and other quality assurance requirements.

PMA approval is not guaranteed, and the FDA may ultimately respond to a PMA application submission with a not approvable determination based on deficiencies in the application and require additional clinical trial or other data that may be expensive and time-consuming to generate and that can substantially delay approval.

If the FDA’s evaluation of the PMA application is favorable, the FDA typically issues an approvable letter requiring the applicant’s agreement to specific conditions, such as changes in labeling, or specific additional information, such as submission of final labeling, in order to secure final approval of the PMA.

If the FDA concludes that the applicable criteria have been met, the FDA will issue a PMA for the approved indications, which can be more limited than those originally sought by the applicant.

The PMA can include post-approval conditions that the FDA believes necessary to ensure the safety and effectiveness of the device, including, among other things, restrictions on labeling, promotion, sale and distribution.

After a device is placed on the market, it remains subject to significant regulatory requirements.

Medical devices may be marketed only for the uses and indications for which they are cleared or approved.

Device manufacturers must also establish registration and device listings with the FDA.

A medical device manufacturer’s manufacturing processes and those of its suppliers are required to comply with the applicable portions of the QSR, which cover the methods and documentation of the design, testing, production, processes, controls, quality assurance, labeling, packaging and shipping of medical devices.

Domestic facility records and manufacturing processes are subject to periodic unscheduled inspections by the FDA.

The FDA also may inspect foreign facilities that export products to the U.S.

health care laws and compliance requirements

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government rebate programs and additional downward pressure on pharmaceutical product prices.

Recently, healthcare reform initiatives culminated in the enactment of the Inflation Reduction Act (“IRA”), in August 2022, which will, among other things, allow the HHS to negotiate the selling price of certain drugs and biologics that CMS reimburses under Medicare Part B and Part D, although only high-expenditure single-source drugs that have been approved for at least 7 years (11 years for biologics) can be selected by CMS for negotiation, with the negotiated price taking effect two years after the selection year.

Recently, healthcare reform initiatives culminated in the enactment of the Inflation Reduction Act (“IRA”), in August 2022, which, among other things, allows the HHS to negotiate the selling price of certain drugs and biologics that CMS reimburses under Medicare Part B and Part D, although only high-expenditure single-source drugs that have been approved for at least 7 years (11 years for biologics) can be selected by CMS for negotiation, with the negotiated price taking effect two years after the selection year.

The negotiated prices, which will first become effective in 2026, will be capped at a statutory ceiling price.

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subsidies for individuals purchasing health insurance coverage in ACA marketplaces through plan year 2025.

These provisions will take effect progressively starting in 2023, although they may be subject to legal challenges.

These provisions began taking effect progressively starting in 2023, although they may be subject to legal challenges.

We expect that additional state and federal healthcare reform measures will be adopted in the future.

The Foreign Corrupt Practices Act

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If we or our potential collaborators fail to comply with applicable foreign regulatory requirements, we may be subject to, among other things, fines, suspension or withdrawal of regulatory approvals, product recalls, seizure of products, operating restrictions and criminal prosecution.

Conducting clinical trials for therapeutic drug candidates in Australia is subject to regulation by Australian governmental entities.

Approval for inclusion in the Australian Register of Therapeutic Goods (the “ARTG”), is required before a pharmaceutical drug product may be marketed in Australia.

Typically, the process of obtaining approval of a new therapeutic drug product for inclusion in the ARTG requires compilation of clinical trial data.

Clinical trials conducted using “unapproved therapeutic goods” in Australia, being those which have not yet been evaluated by the Therapeutic Goods Administration (the “TGA”), for quality, safety and efficacy must occur pursuant to either the Clinical Trial Notification (“CTN”), or Clinical Trial Exemption (“CTX”), process.

The CTN process broadly involves submission to a Human Research Ethics Committee (the “HREC”) of all material relating to the proposed clinical trial after completion of pre-clinical laboratory and animal testing.

The institution or organization at which the clinical trial will be conducted (the “Approving Authority”) then gives the final approval for the conduct of the clinical trial at the site, having due regard to the advice from the HREC.

After receiving final approval, CTN clinical trials cannot commence until the clinical trial has been notified to the TGA.

Following approval, responsibility for all aspects of the trial conducted under a CTN application remains with the HREC of each investigator’s institution.

Under the CTX process a sponsor submits an application to conduct a clinical trial to the TGA for evaluation and comment and a sponsor cannot commence a CTX clinical trial until written advice has been received from the TGA regarding the application and approval for the conduct of the clinical trial has been obtained from an ethics committee and the institution at which the clinical trial will be conducted.

In each of the CTN or CTX process, it is required that adequate and well-controlled clinical trials demonstrate the quality, safety and efficacy of the therapeutic product, evidence is compiled which demonstrates that the manufacture of the therapeutic drug product complies with the principles of cGMP and manufacturing and clinical data is derived to submit to the Australian Committee on Prescription Medicines.

The Australian Committee on Prescription Medicines then makes recommendations to the TGA and the TGA ultimately decides whether to include the therapeutic drug product in the ARTG.

The TGA has developed guidelines for a CTN.

Under the CTN process, all material relating to the proposed clinical trial is submitted directly to the HREC of each institution at which the clinical trial is to be conducted.

An HREC is an independent review committee set up under guidelines of the Australian National Health and Medical Research Council.

The role of an HREC is to ensure the protection of rights, safety and wellbeing of human subjects involved in a clinical trial by, among other things, reviewing, approving and providing continuing review of trial protocols and amendments, and of the methods and material to be used in obtaining and documenting informed consent of the trial subjects.

The TGA is formally notified by submission of a CTN application but does not review the safety of the drug or any aspect of the proposed trial.

The standards for clinical research in Australia are set by the TGA and the National Health and Medical Research Council, and compliance with GCP is mandatory.

Guidelines, such as those promulgated by the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (“ICH”), are required across all fields, including those related to pharmaceutical quality, nonclinical and clinical data requirements and study designs.

The basic requirements for preclinical data to support a first-in- human study under ICH guidelines are applicable in Australia.

Requirements related to adverse event reporting in Australia are similar to those required in other major jurisdictions.

Employees and Human Capital Resources

As of December 31, 2022, we had 96 full-time employees.

As of December 31, 2023, we had 117 employees.

Of these employees, 85 were primarily engaged in research and development activities and 29 held a doctorate degree such as an M.D., Ph.D., or PharmD.

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What changed 10-K

Item 1. Business