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Item 1. Business

2022-03-01 compared with 2021-03-25 · 165 added, 133 removed, 386 unchanged (44% of the section changed)

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Existing protein engineering treatments generally involve the modification of native proteins.

With our proprietary platform we design completely new protein structures from the ground up, capable of demonstrating specific biological properties.

With our proprietary platform, which we refer to as our Neoleukin platform, we design new protein scaffolds from the ground up, capable of demonstrating specific biological properties.

Through this method we are able to produce proteins that, while resembling native proteins, may have novel molecular interfaces, differential activation of specific cell types, increased stability, or improved biodistribution compared to native proteins in order to deliver greater therapeutic benefit.

De novo proteins have the capacity to be cytokine receptor agonists, antagonists, or result in conditional activation of specific cytokine receptors such that they may regulate inflammation or the immune response to cancer.

We are initially focused on key cytokine mimetics, which we refer to as Neoleukin de novo cytokine mimetics.

Neoleukin de novo cytokine mimetics can be modified to adjust affinity, thermodynamic stability, resistance to biochemical modification, pharmacokinetic characteristics, and targeting to tumor or inflamed tissues.

Our lead product candidate, NL-201, is a de novo protein designed to mimic the therapeutic activity of the cytokines interleukin-2, or IL-2, and interleukin-15, or IL-15, for the potential treatment of various types of cancer, including renal cell carcinoma, or RCC, and melanoma, while limiting the toxicity caused by the preferential binding of native IL-2 and IL-15 to non-target cells.

Our lead product candidate, NL-201, is a de novo protein designed to mimic the therapeutic activity of the cytokines interleukin-2, or IL-2, and interleukin-15, or IL-15, for the potential treatment of various types of cancer, including renal cell carcinoma, or RCC, melanoma, and hematological malignancies, while limiting the toxicity caused by the preferential binding of native IL-2 and IL-15 to non-target cells.

In preclinical studies, a closely-related precursor to NL-201 demonstrated higher levels of activity and lower toxicity in multiple murine solid tumor syngeneic models as compared to recombinant, native IL-2.

Neoleukin/Aquinox Merger

On August 8, 2019, Neoleukin Therapeutics, Inc., or Former Neoleukin, completed its merger with Aquinox Pharmaceuticals, Inc., or Aquinox, in accordance with the terms of the Agreement and Plan of Merger dated August 5, 2019, or the Merger Agreement by and among Aquinox, Former Neoleukin and Apollo Sub, Inc., a wholly-owned subsidiary of Aquinox.

Pursuant to the Merger Agreement, Apollo Sub, Inc.

merged with and into Former Neoleukin, with Former Neoleukin surviving the Merger as a wholly-owned subsidiary of Aquinox, referred to herein as the Merger.

Upon completion of the Merger, Aquinox was renamed Neoleukin Therapeutics, Inc.

and Former Neoleukin was renamed Neoleukin Corporation .

De Novo Protein Design Technology

Our proprietary technology, which we refer to as our Neoleukin platform, uses a set of advanced computational algorithms and methods to design functional de novo proteins.

Our Neoleukin platform uses a set of advanced computational algorithms and methods to design functional de novo proteins.

A protein is generally defined as one or more chains of covalently-linked amino acids – totaling at least 50 amino acids – that assemble into a 3-dimensional structure.

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however this is still only a small subset of all possible amino acid sequences that can be assembled to form a protein.

While protein engineering to date has largely been conducted through the modification of native proteins, with our platform we are able to explore the full sequence space, guided by the physical principles that underlie protein folding, and design functional proteins from the ground up.

While protein engineering to date has largely been conducted through the modification of native proteins, with our Neoleukin platform we are able to explore the full sequence space, guided by the physical principles that underlie protein folding, and design functional proteins from the ground up.

Our de novo proteins fit the above definition of a protein, but, unlike native proteins, are designed using our proprietary computational algorithms and methods.

Successful de novo protein design is a cutting-edge process that requires both the advanced computational tools of our proprietary platform and deep insight into how a sequence of amino acids will fold into a stable 3-dimensional protein.

To design a Neoleukin de novo cytokine mimetic using the Neoleukin platform, we begin with an accurate model of the biological target.

Successful de novo protein design is a cutting-edge process that requires both the advanced computational tools and deep insight into how a sequence of amino acids will fold into a stable 3-dimensional protein.

To design a Neoleukin de novo cytokine mimetic using our Neoleukin platform, we begin with an accurate model of the biological target.

This is typically a high-resolution crystal structure but may instead be a computationally-modeled structure.

Then, critical points of contact between molecular interfaces are identified so that essential interactions can be maintained or strengthened, and undesirable interactions can be avoided.

Next, we use a computational algorithm to build idealized 3-dimensional topologies.

Next, we use a computational algorithm to build idealized 3-dimensional topologies of the biological target and the Neoleukin de novo cytokine mimetic.

Finally, we use a separate computational algorithm to select amino acids for each position within the idealized 3-dimensional topologies that maximizes interactions at the desired interface and the thermodynamic stability of the resulting protein.

The resulting amino acid sequences are then expressed in bacteria, tested in the laboratory, and further modified to optimize the final sequence.

These amino acid sequences are then expressed in bacteria, tested in our laboratory, and further modified to optimize the final sequence.

The resulting protein is unlike anything that exists in nature and can be fine-tuned to improve on the desired biological activity.

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Furthermore, we believe that the Neoleukin platform can also be used to generate de novo proteins that inhibit activation of specific receptors, a property that could be valuable for treatment of inflammatory or autoimmune conditions.

Computational design of therapeutic proteins is in a very early stage.

Computational design of therapeutic proteins is in a very early stage of development.

The potential is vast, and we are focused on continuing to improve the technology and realizing the tremendous potential of de novo protein design to improve human health.

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• Develop proprietary de novo protein immunotherapies for the treatment of cancer and inflammatory conditions;

• Become the leader in de novo protein design for therapeutic applications by strengthening our intellectual property and know-how;

• Collaborate with leading biotechnology, pharmaceutical, and academic partners to expand the scope of our platform.

• Become the leader in de novo protein design for therapeutic applications by strengthening our intellectual property, including know-how;

• Collaborate with leading biotechnology, pharmaceutical, and academic partners to expand the scope and application of our platform.

The key elements of our strategy are:

• Rapidly advance NL-201 to clinical proof-of-concept .

NL-201 is our lead product candidate and we believe it will be the first entirely de novo therapeutic protein to be evaluated in a clinical setting.

We submitted a Clinical Trial Notification in Australia and an Investigational New Drug (or IND) Application to the FDA in the fourth quarter of 2020.

On January 7, 2021, we received a clinical hold letter from the FDA related to the IND.

We are currently working to address the FDA's comments related to development of a new assay that more precisely measures the amount of protein being administered and demonstration with this assay that dose and administration procedures will accurately deliver the intended dose, as well as addressing the FDA's other requests not related to the clinical hold.

NL-201 is our lead product candidate and we believe it is the first entirely de novo therapeutic protein to be evaluated in a clinical setting.

In 2021, we initiated a Phase 1 clinical trial in patients with advanced, relapsed, or refractory solid tumors.

The Phase 1 trial is currently ongoing with interim data expected in the second half of 2022.

We also plan to expand our ongoing trial of NL-201 by adding a combination arm with Merck's KEYTRUDA ® (pembrolizumab) in mid-2022.

In addition, we plan to initiate a Phase 1 clinical trial in hematological malignancies with NL-201 in 2022.

• Generate preclinical data for additional product candidates.

Our research activities are currently focused on the development of novel de novo interleukin receptor agonists and antagonists to expand our pipeline.

Our research activities are currently focused on the development of novel de novo cytokine receptor agonists and antagonists to expand our pipeline.

We are currently optimizing and evaluating several early research projects as potential clinical candidates.

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We believe that there will be a rapid evolution in the enabling technology, such that it will be feasible to design more complex and dynamic proteins in the future.

We intend to devote a significant amount of resources to building our computational talent and infrastructure in order to position Neoleukin as a leader in the design and development of de novo protein therapeutics.

We intend to devote a significant amount of resources to building our talent, methods, and infrastructure in order to position Neoleukin as a leader in the design and development of de novo protein therapeutics.

• Build partnerships to leverage the Neoleukin platform.

There is substantial interest in the field of de novo protein design for therapeutic applications.

We intend to seek potential partners that can provide additional resources and expertise to further advance our pipeline and broaden our potential targets.

We intend to seek partners that can provide additional resources and expertise to further advance our pipeline and broaden our potential targets.

We may also strategically pursue one or more collaborations to design, out-license, or co-develop de novo proteins.

Our lead product candidate, NL-201, is an IL-2/IL-15 immunotherapy designed to eliminate binding to the alpha subunit of the IL-2 receptor (also known as CD25) while maintaining high-affinity binding to the beta and gamma subunits.

In multiple preclinical animal models, a precursor to NL-201 demonstrated substantial anti-tumor activity without detectable binding to CD25, as compared to native IL-2.

Following these preclinical studies, we further refined our precursor to extend its half-life, resulting in our NL-201 product candidate.

We have since completed multi-dose, non-GLP and GLP toxicology studies of NL-201 in rats and non-human primates.

Our lead product candidate, NL-201, is an IL-2/IL-15 immunotherapy designed to eliminate binding to the alpha subunit of the IL-2 receptor (also known as CD25) while enhancing binding to the beta and gamma subunits.

In multiple preclinical animal models, a precursor to NL-201, demonstrated substantial antitumor activity without detectable binding to CD25, as compared to native IL-2.

Following these preclinical studies, we further refined our precursor to extend its half-life, resulting in the NL-201 product candidate.

We have since completed multi-dose, non-GLP and GLP toxicology studies of NL-201 in rats and non-human primates, as well as initiated a first in-human clinical trial.

This included completion of GLP in-life dosing with no unexpected toxicities observed.

NL-201 is intended to be used as either a single-agent or in combination with complementary therapeutic modalities,

including checkpoint inhibitors.

In addition, we believe NL-201 holds promise in combination with allogenic cell therapy to expand and maintain populations of transplanted CAR-T and natural killer, or NK, cells.

IL-2 is one of the few immuno-oncology drugs proven to work as a single agent.

IL-2 has a demonstrated mechanism of action for treating tumors;

NL-201 is intended to be used as either a single-agent or in combination with complementary therapeutic modalities, including checkpoint inhibitors.

In addition, we believe NL-201 holds promise in combination with cell therapy to expand and maintain populations of transplanted CAR-T and natural killer, or NK, cells.

IL-2 is one of the few immuno-oncology drugs with demonstrated activity as a single agent.

IL-2 has a confirmed mechanism of action for treating tumors;

however, it has encountered issues as a therapeutic due to the biased activation of cells that contain CD25.

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Due to IL-2’s potential for high toxicity, with vascular leak syndrome and cytokine storm being frequent side effects, and reduced efficacy over time, its use as a therapeutic has been limited.

Further, low-dose treatments have generally been insufficient to demonstrate activity.

Further, low-dose treatments have generally been insufficient to demonstrate therapeutic activity.

While the problem posed by IL-2 is well understood, it has been difficult to modify native IL-2 to retain potent activation of IL-2 receptor signaling while eliminating binding to CD25.

Instead of modifying native IL-2, computational methods were used to design a new sequence with the proper intermolecular interactions to efficiently bind the beta and gamma subunits while eliminating CD25 binding in preclinical models.

As opposed to traditional recombinant human, or humanized, protein therapeutics, de novo proteins are entirely novel sequences with limited homology to native proteins.

While there is a potential that patients may mount an anti-drug immune response against NL-201, we believe that this risk is mitigated by several factors, including the stability of the protein and its resistance to proteolytic degradation.

As opposed to traditional recombinant protein therapeutics, de novo proteins are entirely novel sequences with limited homology to native proteins.

While there is a potential that patients may mount an anti-drug immune response against NL-201, we believe that this risk may be mitigated by several factors, including the stability of the protein and its resistance to proteolytic degradation.

Immunotherapy Market Overview

Over the past several decades, the potential of the immune system to control and/or eliminate cancer has been better understood and appreciated.

Immunotherapies, including allogenic stem cell transplantation, checkpoint inhibitors, and cellular therapies have led to impressive improvements in patient outcomes.

Immunotherapy is one of the fastest growing segments of the oncology market.

Immune checkpoint inhibitors are one of the most widely used classes of cancer immunotherapy.

Immunotherapies, including allogeneic stem cell transplantation, checkpoint inhibitors, and cellular therapies have led to impressive improvements in patient outcomes.

Immunotherapy is one of the fastest growing segments of the oncology market and immune checkpoint inhibitors are one of the most widely used classes of cancer immunotherapy.

Checkpoint inhibitors promote an anti-cancer immune response by blocking inhibitory signals between cancer cells and the immune microenvironment.

Patients with metastatic cancers, who previously had uniformly poor prognoses, now have the opportunity to achieve durable responses with checkpoint inhibitors.

The initial drug in this class, ipilimumab, was approved in 2011.

Since that time, many additional checkpoint inhibitors have been approved.

Patients with metastatic cancers, who previously had generally poor prognoses, now have the opportunity to achieve durable responses with checkpoint inhibitors.

The initial drug in this class, ipilimumab, was approved by the United States Food and Drug Administration, or FDA, in 2011.

Since that time, many additional checkpoint inhibitors have been approved by the FDA.

In addition to checkpoint inhibitors, other notable cancer immunotherapies expected to improve cancer outcomes over the next decade include bi-specific T-cell engagers, immune agonists, and cellular therapies.

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Despite achieving success in a subset of patients, checkpoint inhibitors often fail to control tumor growth.

In addition, some patients do not tolerate checkpoint inhibitors.

In addition, some patients do not tolerate checkpoint inhibitor therapy regimens.

While checkpoint inhibitors work to block the mechanisms by which malignant cells evade immunological surveillance by anti-cancer T cells, they are less effective in patients who lack a favorable tumor microenvironment, expression of the inhibitory ligand, or sufficient tumor-specific antigens.

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However, significant toxicity has resulted in multiple boxed warnings in the labeling, including a requirement that administration occur in the hospital under supervision of an experienced physician.

As a result of these toxicities, aldesleukin is not frequently used in the clinic.

As a result of these toxicities, aldesleukin is not frequently used clinically.

In addition, aldesleukin has a relatively modest rate of durable remissions, potentially because it preferentially stimulates the proliferation of regulatory T cells, which can inhibit the antitumor response.

We believe there is a clear clinical need for an agent that stimulates an immunological response to cancer with greater selectivity and less toxicity than aldesleukin.

Initial Clinical Development Plan

We submitted our IND in December 2020.

On January 7, 2021, we received a clinical hold letter from the U.S.

Food and Drug Administration (FDA) related to our Investigational New Drug (IND) Application to begin a Phase 1 clinical program for NL-201.

The FDA has informed us that we need to develop a new assay that more precisely measures the amount of protein being administered and demonstrate with this assay that dose and administration procedures will accurately deliver the intended dose of NL-201.

The FDA also had additional requests not related to the clinical hold to be addressed by amendment of the IND.

We are working diligently to address the FDA’s requests, and currently expect to resolve the clinical hold as well as to begin enrollment of patients in the first half of 2021;

however, we do not have a definitive timeline as to when we will have clearance to proceed with clinical trials.

Ongoing Clinical Development

NL-201 is currently being evaluated in a Phase 1 clinical trial in advanced solid tumors.

The Phase 1 clinical trial is planned to enroll up to 120 patients with advanced, relapsed, or refractory solid tumors.

Patients will receive monotherapy, intravenous NL-201 and may continue treatment until disease progression.

The trial is assessing safety, pharmacokinetics, pharmacodynamics, immunogenicity, and antitumor activity.

When the recommended dose and schedule are determined, we expect to enroll indication-specific expansion cohorts of patients with renal cell carcinoma and melanoma.

The trial is being conducted at multiple sites in North America and Australia.

In addition to our ongoing Phase 1 clinical trial of NL-201 for advanced solid tumors, we plan to initiate a Phase 1 clinical trial of NL-201 in hematological malignancies in 2022.

NL-201 has also shown potential for enhanced antitumor activity in preclinical studies when combined with other therapies such as checkpoint inhibitors, CAR-T cell therapy, and tumor-targeting antibodies.

On January 10, 2022, we announced a clinical collaboration with Merck to evaluate NL-201 in combination with KEYTRUDA ® (pembrolizumab).

We plan to amend the ongoing solid tumor trial in order to add a pembrolizumab combination arm with up to an additional 132 patients.

UW License Agreement

On July 8, 2019, Former Neoleukin entered into an Exclusive License Agreement with the University of Washington, or UW, under which UW (on behalf of itself and Stanford University) granted us an exclusive worldwide license under certain patent rights, to make, have made, use, offer to sell, sell, offer to lease or lease, import, export or otherwise offer to dispose of licensed products in all fields of use, and a nonexclusive worldwide license to use certain know-how.

The foregoing licenses are able to sublicense by us without UW’s consent, subject to certain limited conditions.

We assumed the benefits and obligations of the Exclusive License Agreement in connection with the completion of the Merger.

The Exclusive License Agreement was amended effective as of July 24, 2020 to, among other things, (i) add a jointly owned patent application directed to de novo cytokine antagonists to the agreement, (ii) specify royalties, milestone payments and sublicense consideration payments payable by Neoleukin for licensed products under certain patent rights related to the jointly owned patent application, (iii) specify the term for achievement of performance milestones for licensed products under certain patents rights related to the jointly owned patent application, and (iv) terminate UW’s right to participate in equity financings.

On July 8, 2019, Neoleukin Therapeutics, Inc., or Former Neoleukin, entered into an Exclusive License Agreement with the University of Washington, or UW, under which UW (on behalf of itself and Stanford University) granted us an exclusive worldwide license under certain patent rights, to make, have made, use, offer to sell, sell, offer to lease or lease, import, export or otherwise offer to dispose of licensed products in all fields of use, and a nonexclusive worldwide license to use certain know-how.

The foregoing licenses may be sublicensed by us without UW’s consent, subject to certain limited conditions.

We assumed the benefits and obligations of the Exclusive License Agreement in connection with the completion of the merger of Former Neoleukin into the Company.

The Exclusive License Agreement was amended effective as of July 24, 2020 to, among other things, (i) add a jointly owned patent application family directed to de novo cytokine antagonists to the agreement, (ii) specify royalties, milestone payments and sublicense consideration payments payable by Neoleukin for licensed products under certain patent rights related to the jointly owned patent application, (iii) specify the term for achievement of performance milestones for licensed products under certain patents rights related to the jointly owned patent application, and (iv) terminate UW’s right to participate in equity financings.

The Exclusive License Agreement was amended a second time, effective as of December 15, 2021 to, among other things, add a second jointly owned patent application family directed to de novo cytokine antagonists to the agreement subject to the same terms of the first jointly owned patent application family.

As consideration for the licensed rights, Former Neoleukin issued shares of common stock to UW, representing five percent of its fully-diluted capitalization on the date on which the Exclusive License Agreement was executed.

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We are obligated to pay royalties on a country-by-country basis until the expiration of the last valid claim within the licensed patent rights in such country.

The agreement will expire upon the expiration of the last valid claim within the licensed patent rights.

We may terminate the agreement upon prior written notice to UW.

UW may terminate the agreement by giving a specified number of days’ notice if we permanently cease operations, become insolvent or similar, or if we challenge the validity of the licensed patent rights.

In addition, UW may terminate the agreement for material breach that is not cured within a specified number of days, which cure period is to be at least doubled if we are proceeding diligently to cure the default.

Research Programs

The Exclusive License Agreement will expire upon the expiration of the last valid claim within the licensed patent rights.

We may terminate the Exclusive License Agreement upon prior written notice to UW.

UW may terminate the Exclusive License Agreement by giving a specified number of days’ notice if we permanently cease operations, become insolvent or similar, or if we challenge the validity of the licensed patent rights.

In addition, UW may terminate the Exclusive License Agreement for material breach that is not cured within a specified number of days, which cure period is to be at least doubled if we are proceeding diligently to cure the default.

Other Research Programs

Beyond our initial focus on NL-201, our research team is working on further applying de novo protein design principles to develop therapeutics to address significant unmet medical needs in immuno-oncology, inflammation, and autoimmunity.

Our research is powered by the Neoleukin platform, our computational framework for developing highly selective, hyper-stable de novo immunomodulatory proteins.

Our research is powered by our Neoleukin platform, which is our computational framework for developing highly selective, hyper-stable de novo immunomodulatory proteins.

Beyond NL-201, we are developing targeted and conditionally active IL-2/IL-15 mimetics, as well as cytokine mimetic programs for other oncology targets.

Our research team is also actively applying the Neoleukin platform to generate de novo receptor agonist and antagonist candidates against multiple targets of interest for inflammatory and autoimmune indications.

Our research team is also actively applying our Neoleukin platform to generate de novo receptor agonist and antagonist candidates against multiple targets of interest for inflammatory and autoimmune indications.

As we validate additional candidates, they will enter our preclinical pipeline.

Due to the COVID-19 public health emergency, we have been investigating the application of our de novo protein technology to prevent or treat SARS-CoV2 infection.

In November 2020, we announced the publication of our scientific work in the journal Science detailing the creation of CTC-445.2d, or NL-CVX1, a de novo protein decoy that is specifically designed to block infection of SARS-CoV-2, the virus causing the ongoing COVID-19 pandemic.

Due to the COVID-19 pandemic, we investigated the application of our de novo protein technology to prevent or treat SARS-CoV-2 virus infection, and, in November 2020, we announced the publication of our scientific work in the journal Science detailing the creation of NL-CVX1, a de novo protein decoy that is specifically designed to block infection of SARS-CoV-2, the virus which causes the COVID-19 disease.

Our findings demonstrated that NL-CVX1 blocks infection of human cells in vitro, even when a high viral burden is used.

Furthermore, intranasal administration of NL-CVX1 protected Syrian hamsters from a lethal dose of SARS-CoV-2.

We are currently planning a first-in-human trial of NL-CVX1, and will continue to evaluate the program as the SARS-CoV-2 landscape evolves.

In June 2021, in response to the evolving COVID-19 therapeutic landscape, including the widespread availability of effective vaccines, we suspended plans to advance this research program into clinical trials.

Intellectual Property

Our intellectual property strategy is centered around robust protection of our pipeline molecules and enabling technologies.

We have licensed rights to patents and patent applications stemming from provisional patent applications that our scientific co-founders authored while they were employees at the University of Washington, or UW.

We have also licensed rights to a provisional patent application that we jointly own with UW.

These patents and patent applications, as applicable, include disclosure and claims encompassing our NL-201 product candidate, the composition of matter of key molecule families, as well as methods of using the computational algorithms that form the basis of the Neoleukin platform.

We have licensed rights to patents and patent applications stemming from provisional patent applications that our scientific co-founders authored while they were employees at UW.

We have also licensed rights to two provisional patent applications that we jointly own with UW.

We have secured an exclusive license from UW to develop and commercialize products covered by these patents and patent applications.

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patents have issued and will expire in 2039, absent any patent term adjustments or extensions.

patent has issued directed to certain targeted Il-2/IL-15 mimetics which will expire in 2039, absent any patent term adjustments or extensions.

Additional patent applications are pending in the United States and world-wide.

Any patents that may issue from these patent applications in-licensed from UW are expected to expire in 2039, absent any patent term adjustments or extensions.

product candidate advances through research and development, we expect to seek to identify and protect new inventions, and have filed applications on new inventions such as methods of administration and combination therapies.

Also, through our research efforts, we anticipate generating intellectual property covering novel compounds and significant improvements on existing molecules.

As our product candidate and other programs advance through research and development, we expect to seek to identify and protect new inventions, and we have filed applications on new inventions such as methods of administration and combination therapies.

Also, through our research efforts, we anticipate generating intellectual property covering novel compounds and improvements on existing molecules.

We expect that patents that result from this new research will remain Neoleukin’s exclusive property, except to the extent jointly developed with third parties.

In addition, our research team is extending and enhancing our computational technology and capabilities.

We intend to protect improvements to the Neoleukin platform through a combination of new patent filings as well as the maintenance of trade secrets.

We intend to protect improvements to the Neoleukin platform through a combination of new patent filings and/or the maintenance of trade secrets, as appropriate.

non-provisional applications and PCT applications that claim the benefit of the priority date of earlier filed provisional applications, when appropriate.

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In geographies that are critical to our commercial success, competitors may also obtain regulatory approvals before us, resulting in our competitors building a strong market position in advance of the entry of our products.

We believe the factors determining the success of our programs will be the efficacy, safety, and convenience of our product candidates.

We believe the primary factors determining the success of our programs will be the efficacy, safety, and convenience of our product candidates.

Manufacturing

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If we choose to build a commercial infrastructure to support marketing in the United States, such commercial infrastructure could be expected to include a targeted sales force supported by sales management, internal sales support, an internal marketing group and distribution support.

To develop the appropriate commercial infrastructure internally, we would have to invest financial and management resources, some of which would have to be deployed prior to any confirmation that NL-201 will be approved.

Government Regulation

As a biopharmaceutical company that operates and anticipates seeking approval for pharmaceutical product candidates in the United States, we are subject to extensive regulation by the U.S.

Food and Drug Administration, or FDA, and other federal, state, and local regulatory agencies.

As a biopharmaceutical company that operates and anticipates seeking approval for pharmaceutical product candidates in the United States, we are subject to extensive regulation by the FDA and other federal, state, and local regulatory agencies.

The Federal Food, Drug, and Cosmetic Act, or the FDC Act, and its implementing regulations set forth, among other things, requirements for the research, testing, development, manufacture, quality control, safety, effectiveness, approval, labeling, storage, record keeping, reporting, distribution, import, export, advertising and promotion of our products.

Our pharmaceutical product candidates must be approved by the FDA before we can commence clinical trials or market those products in the United States.

Although the discussion below focuses on regulation in the United States, we conduct research activities and anticipate seeking approval for, and marketing of, our products in other countries and regions, such as Europe.

Generally, our activities in other countries will be subject to regulation that is similar in nature and scope as that imposed in the United States, although there can be important differences.

Additionally, some significant aspects of regulation in Europe are addressed in a centralized way through the EMA, but country-specific regulation remains essential in many respects.

Additionally, some significant aspects of regulation in Europe are addressed in a centralized way through the European Medicines Agency, or EMA, but country-specific regulation remains essential in many respects.

The process of obtaining regulatory marketing approvals and the subsequent compliance with appropriate federal, state, local and foreign statutes and regulations require the expenditure of substantial time and financial resources.

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• completion of preclinical laboratory tests, animal studies and formulation studies in compliance with the FDA’s Good Laboratory Practices regulations;

• submission to the FDA of an IND, which must become effective before human clinical trials may begin;

• submission to the FDA of an Investigational New Drug Application, or IND, which must become effective before human clinical trials may begin;

• approval by an IRB at each clinical site before each trial may be initiated;

• performance of adequate and well-controlled clinical trials in accordance with federal regulations and with current good clinical practices, or GCPs, to establish the safety and efficacy of the investigational drug product for each targeted indication;

• development of manufacturing processes to ensure the product candidate’s identity, strength, quality, purity, and potency;

• submission of BLA to the FDA;

• satisfactory completion of an FDA inspection of the manufacturing facilities at which the investigational product is produced to assess compliance with cGMP, and to assure that the facilities, methods and controls are adequate;

• satisfactory completion of an FDA inspection of the manufacturing facilities at which the investigational product is produced to assess compliance with the FDA's Current Good Manufacturing Practice Regulations, or cGMP, and to assure that the facilities, methods and controls are adequate;

• satisfactory completion of FDA inspection of investigator sites;

• FDA review and approval of the BLA.

With the enactment of the Biologics Price Competition and Innovation Act of 2009, or BPCIA, an abbreviated pathway for the approval of biosimilar and interchangeable biological products was created.

The abbreviated regulatory pathway establishes legal authority for the FDA to review and approve biosimilar biologics, including the possible designation of a biosimilar as

interchangeable based on its similarity to an existing reference product.

The abbreviated regulatory pathway establishes legal authority for the FDA to review and approve biosimilar biologics, including the possible designation of a biosimilar as interchangeable based on its similarity to an existing reference product.

Notwithstanding minor differences in clinically inactive components, biosimilarity sufficient to reference a prior FDA-approved product requires a high similarity to the reference product and no clinically meaningful differences between the biological product and the reference product in terms of safety, purity, potency, mechanism of action, conditions of use, route of administration, and dosage formulation.

Biosimilarity must be shown through analytical studies, animal studies, and at least one clinical trial, absent a waiver by the FDA.

Under the BPCIA, an application for a biosimilar product cannot be approved by the FDA until 12 years after licensure date of the reference product licensed under a BLA.

No application for a biosimilar can be submitted for four years from the licensure date of the reference product.

However, certain changes and supplements to an approved BLA, and subsequent applications filed by the same sponsor, manufacturer, licensor, predecessor in interest, or other related entity do not qualify for the 12-year exclusivity period.

Preclinical tests include laboratory evaluation of product chemistry, formulation, and toxicity, as well as animal trials to access the characteristics and potential safety and efficacy of the product.

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The manufacturing process must be capable of consistently producing quality batches of the product candidate and, among other things, the manufacturer must develop methods for testing the identity, strength, quality, purity and potency of the final product.

Additionally, appropriate packaging must be selected and

tested, and stability studies must be conducted to demonstrate that the product candidate does not undergo unacceptable deterioration over its shelf life.

Additionally, appropriate packaging must be selected and tested, and stability studies must be conducted to demonstrate that the product candidate does not undergo unacceptable deterioration over its shelf life.

Assuming successful completion of all required testing in accordance with all applicable regulatory requirements, a BLA is submitted to the FDA to request market approval for the product in specified indications.

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A BLA supplement for a new indication typically requires clinical data similar to that in the original application, and the FDA uses the same procedures and actions in reviewing BLA supplements as it does in reviewing BLAs.

Advertising and Promotion

The FDA and other federal regulatory agencies closely regulate the marketing and promotion of drugs through, among other things, standards and regulations for direct-to-consumer advertising, communications regarding unapproved uses, industry-sponsored scientific and educational activities, and promotional activities involving the Internet.

A product cannot be commercially promoted before it is approved.

After approval, product promotion can include only those claims relating to safety and effectiveness that are consistent with the labeling approved by the FDA.

Healthcare providers are permitted to prescribe drugs for “off-label” uses—that is, uses not approved by the FDA and therefore not described in the drug’s labeling—because the FDA does not regulate the practice of medicine.

However, FDA regulations impose stringent restrictions on manufacturers’ communications regarding off-label uses.

Broadly speaking, a manufacturer may not promote a drug for off-label use, but may engage in non-promotional, balanced communication regarding off-label use under specified conditions.

Failure to comply with applicable FDA requirements and restrictions in this area may subject a company to adverse publicity and enforcement action by the FDA, the U.S.

Department of Justice (DOJ), or the Office of the Inspector General of HHS, as well as state authorities.

This could subject a company to a range of penalties that could have a significant commercial impact, including civil and criminal fines and agreements that materially restrict the manner in which a company promotes or distributes drug products.

Disclosure of Clinical Trial Information

Furthermore, should new safety information arise, additional testing, product labeling, or FDA notification may be required.

Sponsors of clinical trials of FDA-regulated products, including biological products, are required to register and disclose certain clinical trial information on the website www.clinicaltrials.gov.

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Pediatric Information

Under the Pediatric Research Equity Act, or PREA, NDAs or BLAs or supplements to NDAs or BLAs must contain data to assess the safety and effectiveness of the biological product for the claimed indications in all relevant pediatric subpopulations and to support dosing and administration for each pediatric subpopulation for which the biological product is safe and effective.

The FDA may grant full or partial waivers, or deferrals, for submission of data.

Unless otherwise required by regulation, PREA does not apply to any biological product with orphan product designation except a product with a new active ingredient that is a molecularly targeted cancer product intended for the treatment of an adult cancer and directed at a molecular target determined by FDA to be substantially relevant to the growth or progression of a pediatric cancer that is subject to an NDA or BLA submitted on or after August 18, 2020.

Under the Pediatric Research Equity Act, or PREA, BLAs or supplements to BLAs must contain data to assess the safety and effectiveness of the product for the claimed indications in all relevant pediatric subpopulations and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective.

The FDA may, on its own initiative or at the request of the applicant, grant full or partial waivers, or deferrals, for submission of data.

Unless otherwise required by regulation, PREA does not apply to any product with orphan product designation except a product with a new active ingredient that is a molecularly targeted cancer product intended for the treatment of an adult cancer and directed at a molecular target determined by FDA to be substantially relevant to the growth or progression of a pediatric cancer.

Fast Track Designation, Accelerated Approval, and Priority Review

A sponsor may seek approval of its product candidate under programs designed to accelerate the FDA’s review and approval of BLAs.

For example, Fast Track Designation may be granted to a drug intended for treatment of a serious or life-threatening disease or condition that has potential to address unmet medical needs for the disease or condition.

The key benefits of fast track designation are more frequent interactions with the FDA and rolling review (submission of portions of an application before the complete marketing application is submitted).

Under Fast Track and the accelerated approval program, the FDA may approve a BLA on the basis of either a surrogate endpoint that is reasonably likely to predict clinical benefit, or on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality, that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit, taking into account the severity, rarity, or prevalence of the condition and the availability or lack of alternative treatments.

Post-marketing studies or completion of ongoing studies after marketing approval are required to verify the drug’s clinical benefit in relationship to the surrogate endpoint or ultimate outcome in relationship to the clinical benefit.

Based on results of the Phase 3 clinical trial(s) submitted in a BLA, upon the request of an applicant, the FDA may grant the BLA a priority review designation, which sets the target date for FDA action on the application at eight months after the BLA submission.

Priority review is granted where there is evidence that the proposed product would be a significant improvement in the safety or effectiveness of the treatment, diagnosis, or prevention of a serious condition.

If criteria are not met for priority review, the application is subject to the standard FDA review period of twelve months after NDA submission.

Priority review designation does not change the scientific/medical standard for approval or the quality of evidence necessary to support approval.

Additional Controls for Biologics

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Post-Approval Regulations

After regulatory approval of a drug is obtained, a company is required to comply with a number of post-approval requirements.

After regulatory approval of a biologic is obtained, a company is required to comply with a number of post-approval requirements.

For example, as a condition of approval of a BLA, the FDA may require post-marketing testing, including Phase 4 clinical trials, and surveillance to further assess and monitor the product’s safety and effectiveness after commercialization.

In addition, as a holder of an approved BLA, a company would be required to report adverse reactions and production problems to the FDA, to provide updated safety and efficacy information, and to comply with requirements concerning advertising and promotional labeling for any of its products.

Also, quality control and manufacturing procedures must continue to conform to cGMP after

approval to assure and preserve the long-term stability of the drug or biological product.

In addition, as a holder of an approved BLA, a company is required to report adverse reactions and production problems to the FDA, to provide updated safety and efficacy information, and to comply with requirements concerning advertising and promotional labeling for any of its products.

Also, quality control and manufacturing procedures must continue to conform to cGMP after approval to assure and preserve the long-term stability of the drug or biological product.

The cGMP requirements apply to all stages of the manufacturing process, including the production, processing, sterilization, packaging, labeling, storage and shipment of the drug product.

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Further, the failure to maintain compliance with regulatory requirements may result in administrative or judicial actions, such as fines, warning or untitled letters, holds on clinical trials, product recalls or seizures, product detention or refusal to permit the import or export of products, refusal to approve pending applications or supplements, restrictions on marketing or manufacturing, injunctions or civil or criminal penalties.

After approval, most changes to the approved product, such as adding new indications or other labeling claims, are subject to prior FDA approval.

Newly discovered or developed safety or effectiveness data may require changes to a product’s approved labeling, including the addition of new warnings and contraindications, and may require the implementation of other risk management measures.

Also, new government requirements, including those resulting from new legislation, may be established, or the FDA’s policies may change, which could delay or prevent regulatory approval of our products under development.

Advertising and Promotion

A product cannot be commercially promoted before it is approved.

After approval, product promotion cannot be false or misleading, and product claims must be adequately substantiated.

However, FDA regulations impose stringent restrictions on manufacturers’ communications regarding off-label uses.

Broadly speaking, a manufacturer may not promote a drug for off-label use, but may engage in non-promotional, balanced communication regarding off-label use under specified conditions.

Failure to comply with applicable FDA requirements and restrictions in this area may subject a company to adverse publicity and enforcement action by the FDA, the U.S.

Department of Justice, or DOJ, or the Office of the Inspector General of the Department of Health and Human Services, or HHS, as well as state authorities.

During all phases of development (pre- and post-marketing), failure to comply with applicable regulatory requirements may result in administrative or judicial sanctions.

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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, or TGA, for quality, safety and efficacy must occur pursuant to either the Clinical Trial Notification, or CTN, or Clinical Trial Exemption, or CTX, process.

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

The CTN process broadly involves:

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The TGA does not review any data relating to the clinical trial;

• the institution or organisation at which the trial will be conducted, referred to as the “Approving Authority” gives the final approval for the conduct of the trial at the site, having due regard to the advice from the HREC;

• the institution or organization at which the trial will be conducted, referred to as the “Approving Authority” gives the final approval for the conduct of the trial at the site, having due regard to the advice from the HREC;

• CTN trials cannot commence until the trial has been notified to the TGA.

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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 role of an HREC is to ensure the protection of rights, safety and well-being 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.

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

Other Healthcare Laws and Compliance Requirements

In the United States, our activities are potentially subject to additional regulation and oversight under other healthcare laws by various federal, state and local authorities in addition to the FDA, including the Centers for Medicare & Medicaid Services, or CMS, other divisions of the United States Department of Health and Human Services (e.g., the Office of Inspector General), the DOJ, and individual U.S.

Other Healthcare, Data Protection, and Privacy Laws and Compliance Requirements

In the United States, our activities are potentially subject to additional regulation and oversight under other healthcare laws by various federal, state and local authorities in addition to the FDA, including the Centers for Medicare & Medicaid Services, or CMS, other divisions of the HHS (e.g., the Office of Inspector General), the DOJ, and individual U.S.

Attorney offices within the DOJ, and state and local governments.

These laws include the federal

Anti-Kickback Statute, which prohibits, among other things, any person or entity, from knowingly and willfully offering, paying, soliciting or receiving any remuneration, directly or indirectly, overtly or covertly, in cash or in kind, to induce or in return for either the referral of an individual, or purchasing, leasing, ordering or arranging for the purchase, lease or order of any good, facility, item or service reimbursable, in whole or part, under Medicare, Medicaid or another federal healthcare program.

These laws include the federal Anti-Kickback Statute, which prohibits, among other things, any person or entity, from knowingly and willfully offering, paying, soliciting or receiving any remuneration, directly or indirectly, overtly or covertly, in cash or in kind, to induce or in return for either the referral of an individual, or purchasing, leasing, ordering or arranging for the purchase, lease or order of any good, facility, item or service reimbursable, in whole or part, under Medicare, Medicaid or another federal healthcare program.

The term remuneration has been interpreted broadly to include anything of value.

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Other companies have been prosecuted for causing false claims to be submitted because of the companies’ marketing of the product for off-label, and thus, non-covered, uses.

In the United States, there are numerous federal and state laws and regulations governing data privacy of personal data and the collection, use, disclosure, and protection of health data, genetic data, consumer data, and children's data.

The federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, created additional federal criminal statutes that prohibit knowingly and willfully executing, or attempting to execute, a scheme to defraud or to obtain, by means of false or fraudulent pretenses, representations or promises, any money or property owned by, or under the control or custody of, any healthcare benefit program, including private third-party payors and knowingly and willfully falsifying, concealing or covering up by trick, scheme or device, a material fact or making any materially false, fictitious or fraudulent statement in connection with the delivery of or payment for healthcare benefits, items or services.

Also, many states have similar fraud and abuse statutes or regulations that apply to items and services reimbursed under Medicaid and other state programs, or, in several states, apply regardless of the payor.

We may also be subject to data privacy and security regulation by both the federal government and the states in which we conduct our business.

HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, or HITECH, and its implementing regulations, imposes requirements relating to the privacy, security and transmission of individually identifiable health information.

HIPAA was amended by the Health Information Technology for Economic and Clinical Health Act, or HITECH, implementing additional regulations and imposing requirements relating to the privacy, security and transmission of individually identifiable health information.

Among other things, HITECH makes certain HIPAA standards directly applicable to business associates—independent contractors or agents of covered entities that receive or obtain protected health information in connection with providing a service on behalf of a covered entity.

HITECH also created four new tiers of civil monetary penalties, amended HIPAA to make civil and criminal penalties directly applicable to business associates, and gave state attorneys general new authority to file civil actions for damages or injunctions in federal courts to enforce the federal HIPAA laws and seek attorney’s fees and costs associated with pursuing federal civil actions.

In addition, state laws govern the privacy and security of health information in specified circumstances, many of which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts.

Additionally, the federal Physician Payments Sunshine Act within the Affordable Care Act, and its implementing regulations, require that certain manufacturers of drugs, devices, biological and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program (with certain exceptions) report annually to CMS information related to certain payments or other transfers of value made or distributed to physicians and teaching hospitals, or to entities or individuals at the request of, or designated on behalf of, the physicians and teaching hospitals, and applicable manufacturers and group purchasing organizations to report annually certain ownership and investment interests held by physicians and their immediate family members and payments or other “transfers of value” to such physician owners and their immediate family members.

In addition, some state laws may more broadly govern the privacy and security of health information in specified circumstances, many of which differ from each other in significant ways from HIPPA/HITECH and may not have the same effect, thus complicating compliance efforts.

We may be subject to privacy and data security regulations and legal requirements in the United States, Europe, and throughout the world as it relates to collection, use, disclosure, and protection of personal information that may be broader than as is required under HIPAA or comparable state laws to HIPAA.

Many of the state laws enable a state attorney general to bring actions and provide private rights of action to consumers as enforcement mechanisms.

There is also heightened sensitivity around certain types of health data, which may be subject to additional protections.

Compliance with these laws requires a flexible privacy framework as they are constantly evolving.

Failure to comply with these laws and regulations could result in government enforcement actions and create liability for us (which could include civil and/or criminal penalties), private litigation, and/or adverse publicity.

Federal regulators, state attorneys general, and plaintiffs' attorneys have been active in this space.

Also, as we become more dependent on information technologies to conduct our operations, cyber incidents, including deliberate attacks and attempts to gain unauthorized access to computer systems and networks, may increase in frequency and sophistication, and we may have legal duties to protect that information and, in the event of a security incident, report to affected individuals and government authority.

Other applicable federal, state, and foreign laws related to privacy and data protection, include, without limitation, the following:

• The Federal Trade Commission, or FTC, and state attorneys general enforce consumer protection laws that prohibit unfair and deceptive acts and practices, including Section 5 of the FTC Act, which creates standards for the collection, use, dissemination, and security of health-related and other non-health-related personal information.

Individual states have comparable unfair and deceptive acts and practices statutes.

• The California Consumer Privacy Act, or CCPA, came into effect in January 2020 and places increased obligations on businesses, including by requiring covered companies to provide new disclosures to California consumers and provide such consumers certain data protection and privacy rights, including the ability to opt-out of certain sales of personal data.

A ballot initiative from privacy rights advocates intended to augment and expand the CCPA called the California Privacy Rights Act, or CPRA, was passed in November 2020 and will take effect in January 2023 (with a look back to January 2022), and modifies the CCPA while also creating a new state agency that will be vested with authority to implement and enforce the CCPA and the CPRA.

• Several states have enacted consumer privacy laws that will take effect in 2023, including:

(1) the Virginia Consumer Data Protection Act that gives new data protection rights to Virginia residents and imposes additional obligations on controllers and processors of personal data similar in scope to the CCPA;

(2) the Colorado Privacy Act, which is set to take effect on July 1, 2023.

As of January 2022, fourteen states have pending legislation under review relating to consumer privacy.

• Domestic laws in all 50 states require businesses to provide notice to customers whose personally identifiable information has been disclosed as a result of a data breach.

• European data protection laws will apply to any clinical trial programs we conduct or research collaborations we enter into in the European Economic Area, or the EEA, the United Kingdom, or the UK, or Switzerland.

These include European Union, or EU, General Data Protection Regulation 2016/679, or GDPR, which applies extra-territorially and imposes onerous requirements on controllers (e.g., sponsors) and processors (e.g., contract research organizations, laboratories) of personal data, including, for example:

(i) accountability and transparency requirements, and enhanced requirements for obtaining valid consent;

(ii) obligations to consider data protection as any new products or services are developed and to limit the amount of personal data processed;

(iii) obligations to comply with data protection rights of data subjects;

and (iv) reporting of personal data breaches to the supervisory authority without undue delay (and no later than 72 hours).

The GDPR and comparable UK and Swiss law also prohibits the international transfer of personal data from the EEA/UK/Switzerland to countries outside of those jurisdictions unless made to a country deemed to have adequate data privacy laws by the European Commission (or as applicable under UK/Swiss authority) or where a data transfer mechanism has been put in place.

Further, the GDPR provides that countries in the EEA may establish their own laws and regulations further restricting the processing of certain personal data, including genetic data, biometric data, and health data.

• In Canada, the Personal Information Protection and Electronic Documents Act, or PIPEDA, and similar provincial laws may impose obligations with respect to processing personal information, including health-related information.

PIPEDA requires companies to obtain an individual’s consent when collecting, using or disclosing that individual’s personal information.

• In Australia, the Privacy Act of 1988 is the primary federal legislation applying to protection of privacy in Australia, applicable to both private and public sectors at the Commonwealth level and outlines Data Subject’s rights, and is supplemented by TGA (Therapeutic Goods Administration).

Additionally, the federal Physician Payments Sunshine Act within the Affordable Care Act, and its implementing regulations, require that certain manufacturers of drugs, devices, biological and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program (with certain exceptions) report annually to CMS information related to certain payments or other transfers of value made or distributed to physicians, physician assistants, certain types of advance practice nurses and teaching hospitals, or to entities or individuals at the request of, or designated on behalf of, the physicians, physician assistants, certain types of advance practice nurses and teaching hospitals, and applicable manufacturers and group purchasing organizations to report annually certain ownership and investment interests held by physicians and their immediate family members and payments or other “transfers of value” to such physician owners and their immediate family members.

In order to distribute products commercially, we must comply with state laws that require the registration of manufacturers and wholesale distributors of pharmaceutical products in a state, including, in some states, manufacturers and distributors who ship products into the state even if such manufacturers or distributors have no place of business within the state.

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The marketability of any products for which we receive regulatory approval for commercial sale may suffer if the government and third-party payors fail to provide adequate coverage and reimbursement.

In addition, an increasing emphasis on managed

care in the United States has increased and will continue to increase the pressure on pharmaceutical pricing.

In addition, an increasing emphasis on managed care in the United States has increased and will continue to increase the pressure on pharmaceutical pricing.

Coverage policies and third-party reimbursement rates may change at any time.

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Furthermore, there has been heightened governmental scrutiny recently over the manner in which manufacturers set prices for their marketed products.

manufacturer patient programs, and reform government program reimbursement methodologies for drug products.

For example, there have been several recent Congressional inquiries and proposed bills designed to, among other things, bring more transparency to drug pricing, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for drug products.

These new laws and initiatives may result in additional reductions in Medicare and other healthcare funding, which could have a material adverse effect on our future customers and accordingly, our financial operations.

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The FCPA also obligates companies whose securities are listed in the United States to comply with accounting provisions requiring us to maintain books and records that accurately and fairly reflect all transactions of the corporation, including international subsidiaries, and to devise and maintain an adequate system of internal accounting controls for international operations.

The Corruption of Foreign Public Officials Act, or CFPOA, prohibits Canadian businesses and individuals from giving or offering to give a benefit of any kind to a foreign public official, or any other person for the benefit of the foreign public official, where the ultimate purpose is to obtain or retain a business advantage.

Under the CFPOA, companies may be liable for the actions of their employees or third-party agents, even if such persons operate outside of Canada.

Human Capital Resources

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Our management team and employees are expected to exhibit and promote honest, ethical and respectful conduct in the workplace.

All of our employees must adhere to a code of conduct that sets standards for appropriate behavior and are required annual training to preventing, identify, report and stop any type of discrimination and harassment.

All of our employees must adhere to a code of conduct that sets standards for appropriate behavior and are required annual training to prevent, identify, report, and stop any type of discrimination and harassment.

Recruitment, hiring, development, training, compensation, and advancement at the Company is based on qualifications, performance, skills and experience without regard to gender, race and ethnicity.

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In addition, we offer every full-time employee the benefit of equity ownership in the company through stock option grants and our employee stock purchase plan.

We also sponsor a 401(k) plan that allows full-time employees to contribute a portion of their salary, subject to

statutory limits.

We also sponsor a 401(k) plan that allows full-time employees to contribute a portion of their salary, subject to statutory limits.

We make matching cash contributions up to a pre-defined annual maximum contribution per employee per year.

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We emphasize employee development and training by providing access to in house development and training sessions.

Employees are encouraged to attend scientific, clinical, and technological meetings and conferences and have access to broad resources they need to be successful.

Employees are encouraged to attend scientific, clinical, and technological meetings and conferences and have access to the broad resources they need to be successful.

The safety, health and wellness of our employees is a top priority.

In response to COVID-19, we have implemented safety protocols including shift work scheduling to reduce number of people in the facility, requirements for the wearing of masks and for social distancing, increased cleaning procedures and readily available hand sanitizer.

These protocols comply with health and safety standards as required by federal, state and local government agencies, taking into consideration guidelines of the Centers for Disease Control and Prevention and other public health authorities.

In addition, the Company has provided work-at-home arrangements for employees who are able to do so.

In response to the COVID-19 pandemic, we have implemented safety protocols, which are reviewed regularly and revised from time to time based on local and federal guidelines.

Since March of 2020, we have made accommodations, including reducing the number and density of people in our facilities, requirements for the wearing of masks and for social distancing, increased cleaning procedures and readily available hand sanitizer.

These protocols are designed to comply with health and safety standards as required by federal, state, and local government agencies, taking into consideration guidelines of the Centers for Disease Control and Prevention and other public health authorities.

In addition, we have provided work-at-home arrangements for employees who are able to do so and require that employees be fully vaccinated and asymptomatic if they are working on site.

Corporate Information

On August 8, 2019, Former Neoleukin, completed its merger with Aquinox Pharmaceuticals, Inc., or Aquinox, in accordance with the terms of the Agreement and Plan of Merger dated August 5, 2019, or the Merger Agreement by and among Aquinox, Former Neoleukin and Apollo Sub, Inc., a wholly-owned subsidiary of Aquinox.

Pursuant to the Merger Agreement, Apollo Sub, Inc.

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and Former Neoleukin was renamed Neoleukin Corporation.

On July 31, 2020, we sold all issued and outstanding capital stock of our Canadian subsidiary, Aquinox Pharmaceuticals (Canada) Inc., to an unrelated third party.

On July 31, 2020, we sold all issued and outstanding capital stock of our Canadian subsidiary, Aquinox Pharmaceuticals (Canada) Inc., or Aquinox Canada, to an unrelated third party.

On December 31, 2020, Neoleukin Corporation was merged into Neoleukin Therapeutics, Inc.

As a result of these transactions, as of December 31, 2020, we have no subsidiaries.

As a result of these transactions, we have consisted of a single operating company since December 31, 2020.

We make available free of charge on our website our annual report on Form 10-K, quarterly reports on Form 10-Q, current reports on Form 8-K and amendments to those reports as soon as reasonably practicable after we electronically file or furnish such materials to the Securities and Exchange Commission, or SEC.

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The information contained on, or that can be accessed through, our website is not part of, and is not incorporated by reference into, this report.

Neoleukin and our other registered or common law trademarks, service marks, or trade names appearing in this Annual Report on Form 10-K are the property of Neoleukin Therapeutics, Inc.

Neoleukin and our other trademarks, service marks, or trade names appearing in this Annual Report on Form 10-K are the property of Neoleukin Therapeutics, Inc.

Other trademarks, service marks, or trade names appearing in this Annual Report on Form 10-K are the property of their respective owners.

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What changed 10-K

Item 1. Business