inbx-20201231


UNITED STATES SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549

			FORM 10-K

(Mark one)

☒ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

For the fiscal year ended December 31, 2020

☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15 (d) OF THE SECURITIES EXCHANGE ACT OF 1934

For the transition period from to

Commission File Number: 001-39452



INHIBRX, INC.

(Exact name of registrant as specified in its charter)

Delaware		82-4257312
(State or other jurisdiction of incorporation or organization)		(I.R.S. Employer Identification Number)

11025 N. Torrey Pines Road, Suite 200
La Jolla, California		92037
(Address of principal executive offices)		(Zip Code)

	(858) 795-4220
(Registrant’s telephone number, including area code)

Securities registered pursuant to Section 12(b) of the Act

Title of each class

Trading symbol(s)

Name of each exchange on which registered

Common Stock, par value $0.0001

INBX

The Nasdaq Global Market

Securities registered pursuant to Section 12(g) of the Act

None

Indicate by check mark if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. Yes ☐ No ☒

Indicate by check mark if the registrant is not required to file reports pursuant to Section 13 or Section 15(d) of the Act. Yes ☐ No ☒

Indicate by check mark whether the registrant: (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such reports); and (2) has been subject to such filing requirements for the past 90 days. Yes ☒ No ☐

Indicate by check mark whether the registrant has submitted electronically and posted on its corporate web site, if any, every Interactive Data File required to be submitted and posted pursuant to Rule 405 of Regulation S-T (§232.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant was required to submit and post such files). Yes ☒ No ☐

Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company, or an emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company” and “emerging growth company” in Rule 12b-2 of the Exchange Act.

Large Accelerated Filer

☐

Accelerated filer

☐

Non-accelerated filer

☒

Smaller reporting company

☒

Emerging growth company

☒

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 7(a)(2)(B) of the Securities Act. ☒

Indicate by check mark whether the registrant has filed a report on and attestation to its management’s assessment of the effectiveness of its internal control over financial reporting under Section 404(b) of the Sarbanes-Oxley Act (15 U.S.C. 7262(b)) by the registered public accounting firm that prepared or issued its audit report. Yes ☐ No ☒

Indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Exchange Act). Yes ☐ No ☒

As of August 31, 2020, the aggregate market value of the registrant’s common stock held by non-affiliates of the registrant was approximately $261.4 million, based on the closing price of the registrant’s common stock on the Nasdaq Global Market of $17.49 per share. The registrant has elected to use August 31, 2020 as the calculation date, as on June 30, 2020 (the last business day of the registrant’s most recently completed second fiscal quarter) the registrant was a privately-held concern.

As of February 28, 2021, the registrant had 37,747,664 shares of common stock outstanding.

Documents Incorporated By Reference

The following documents (or parts thereof) are incorporated by reference into the following parts of this Form 10-K: Certain information required in Part III of this Annual Report on Form 10-K is incorporated from the Registrant’s Proxy Statement for the 2021 Annual Meeting of Stockholders to be filed with the Securities and Exchange Commission.

INHIBRX, INC.
ANNUAL REPORT ON FORM 10-K
For the Year Ended December 31, 2020


	TABLE OF CONTENTS
		PAGE
Special Note Regarding Forward-Looking Statements		1
Part I.		3
Item 1.	Business	3
Item 1A.	Risk Factors	60
Item 2.	Properties	107
Item 3.	Legal Proceedings	108
Item 4.	Mine Safety Disclosures	109

Part II.		110
Item 5.	Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities	110
Item 6.	Selected Financial Data	111
Item 7.	Management’s Discussion and Analysis of Financial Condition and Results of Operations	112
Item 7A.	Quantitative and Qualitative Disclosures About Market Risk	126
Item 8.	Financial Statements and Supplementary Data	127
Item 9.	Changes in and Disagreements With Accountants on Accounting and Financial Disclosure	165
Item 9A.	Controls and Procedures	166
Item 9B.	Other Information	167

Part III		168
Item 10.	Directors, Executive Officers and Corporate Governance	168
Item 11.	Executive Compensation	168
Item 12.	Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters	168
Item 13.	Certain Relationships and Related Transactions, and Director Independence	168
Item 14.	Principal Accounting Fees and Services	168

Part IV.		169
Item 15.	Exhibits and Financial Statement Schedules	169
Item 16.	Form 10-K Summary	172

Signatures		172

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SPECIAL NOTE REGARDING FORWARD-LOOKING STATEMENTS

This Annual Report on Form 10-K, or this Annual Report of Inhibrx, Inc., or Inhibrx, or the Company (also referred to as “we,” “us,” and “our”) contains forward-looking statements that involve risks and uncertainties. Except as otherwise indicated by the context, references in this Annual Report to “we,” “us” and “our” are to the consolidated business of the Company. All statements other than statements of historical facts contained in this Annual Report are forward-looking statements. In some cases, you can identify forward-looking statements by words such as “anticipate,” “believe,” “contemplate,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “possible,” “potential,” “predict,” “project,” “design,” “seek,” “should,” “target,” “will,” “would,” or the negative of these words or other comparable terminology. These forward-looking statements include, but are not limited to, statements about:

•the initiation, timing, progress and results of our research and development programs as well as our preclinical studies and clinical trials;

•our ability to advance therapeutic candidates into, and successfully complete, clinical trials;

•our interpretation of initial, interim or preliminary data from our clinical trials, including interpretations regarding disease control and disease response;

•the timing or likelihood of regulatory filings and approvals;

•the commercialization of our therapeutic candidates, if approved;

•the pricing, coverage and reimbursement of our therapeutic candidates, if approved;

•our ability to utilize our technology platform to generate and advance additional therapeutic candidates;

•the implementation of our business model, strategic plans for our business and therapeutic candidates;

•our ability to successfully manufacture our therapeutic candidates for clinical trials and commercial use, if approved;

•our ability to contract with third-party suppliers and manufacturers and their ability to perform adequately;

•the scope of protection we are able to establish and maintain for intellectual property rights covering our therapeutic candidates;

•our ability to enter into strategic partnerships and the potential benefits of such partnerships;

•our estimates regarding expenses, capital requirements and needs for additional financing;

•our financial performance;

•our expectations regarding the impact of the COVID-19 pandemic on our business;

•our and our third party partners and service providers’ ability to continue operations and advance our therapeutic candidates through clinical trials and the ability of our third party manufacturers to provide the required raw materials, antibodies and other biologics for our preclinical research and clinical trials in light of the COVID-19 pandemic and the recent political developments in Hong Kong;

•our ability to retain the continued service of our key professionals and to identify, hire and retain additional qualified professionals; and

•developments relating to our competitors and our industry.

These forward-looking statements are subject to a number of risks, uncertainties and assumptions, including those described in the section titled “Risk Factors” elsewhere in this Annual Report. Moreover, we operate in a very competitive and rapidly changing environment, and new risks emerge from time to time. It is not possible for our management to predict all risks, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements we may make. In light of these risks, uncertainties and assumptions, the forward-looking events and circumstances discussed in this Annual Report may not occur and actual results could differ materially and adversely from those anticipated or implied in the forward-looking statements. In addition, statements that “we believe” and similar statements reflect our beliefs and opinions on the relevant subject. These statements are based upon information available to us as of the date of this Annual Report, and while we believe such information forms a reasonable basis for such statements, such information may be limited or incomplete, and our statements should not be read to indicate that we have conducted an exhaustive inquiry into, or review of, all potentially available relevant information. These statements are inherently uncertain and investors are cautioned not to unduly rely upon these statements.

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You should not rely upon forward-looking statements as predictions of future events. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee that the future results, levels of activity, performance or events and circumstances reflected in the forward-looking statements will be achieved or occur. We undertake no obligation to update publicly any forward-looking statements for any reason after the date of this Annual Report to conform these statements to new information, actual results or to changes in our expectations, except as required by law.

You should read this Annual Report and the documents that we file with the Securities and Exchange Commission, or the SEC, with the understanding that our actual future results, levels of activity, performance, and events and circumstances may be materially different from what we expect.

This annual report includes trademarks, tradenames and service marks that are the property of other organizations. Solely for convenience, trademarks and tradenames referred to in this annual report appear without the ® and ™ symbols, but those references are not intended to indicate, in any way, that we will not assert, to the fullest extent under applicable law, our rights, or that the applicable owner will not assert its rights, to these trademarks and tradenames.

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Part I.

Item 1. Business.

Overview

We are a clinical-stage biotechnology company with a pipeline of novel biologic therapeutic candidates, developed using our protein engineering expertise and proprietary single domain antibody, or sdAb, platform. Our sdAb platform allows us to pursue validated targets with clinical promise, but where other antibody and biologic based approaches have failed. Highly modular, our sdAbs can be combined with precise valencies and multiple specificities, creating therapeutic candidates designed to be capable of enhanced cell signaling, conditional activation or combined synergistic functions.

We currently have four programs in ongoing clinical trials, with the most advanced expected to initiate a registration-enabling trial in mid-2021. Three of these programs are for the treatment of various cancers, and one for the treatment of Alpha-1 Antitrypsin Deficiency, or AATD. Our most advanced therapeutic candidate, INBRX-109, is a tetravalent death receptor 5, or DR5, agonist currently being evaluated in patients diagnosed with difficult-to-treat cancers, such as chondrosarcoma, synovial sarcoma, mesothelioma and pancreatic adenocarcinoma. We plan to submit an amended Investigational New Drug Application, or IND, to the U.S. Food and Drug Administration, or the FDA, for INBRX-109 during March 2021. We expect to initiate a registration-enabling trial evaluating INBRX-109 in patients diagnosed with conventional chondrosarcoma around mid-2021. INBRX-106 is a hexavalent OX40 agonist, currently being investigated as a single agent and in combination with Keytruda, in patients with locally advanced or metastatic solid tumors. Both INBRX-109 and INBRX-106 programs are designed to achieve target agonism through precise control of therapeutic valency. INBRX‑105 is a conditional 4-1BB agonist, currently being investigated in patients with locally advanced or metastatic solid tumors, as a single agent and initiating in combination with Keytruda during the second quarter of 2021. Our fourth program, INBRX-101, is an optimized, recombinant alpha 1 antitrypsin, or AAT, augmentation therapy for AATD. We anticipate additional data releases from all four of our clinical programs in 2021.

Our Pipeline

We have developed a diverse pipeline of therapeutic candidates that are specifically designed to leverage the power of our core sdAb platform and protein engineering expertise, as shown below:

INBRX-109

INBRX-106

INBRX-105

INBRX-101

Tetravalent DR5 agonist

Hexavalent OX40 agonist

PD-L1x4-1BB tetravalent conditional agonist

AAT-Fc fusion protein

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Program

Therapeutic Area

Target(s)/Format

STAGE OF DEVELOPMENT

Anticipated Next Milestones

Preclinical

Phase 1

Phase 2

Phase 3

INBRX-109*

Oncology

DR5
Tetravalent Agonist

• Initiation of Trials-

◦Registration-enabling Phase 2 trial in conventional chondrosarcoma –Mid-2021^

◦Ewing combination cohort – Mid-2021

• Initial Data-

◦Mesothelioma and pancreatic adenocarcinoma chemotherapy combination cohorts – Q4 2021

◦Synovial sarcoma cohort (single agent) – 2H 2021

◦Ewing combination cohort –1H 2022

INBRX-106**

Oncology

OX40
Hexavalent Agonist

• Initial Data-

◦ Escalation with Keytruda – Q3 2021

◦ Expansion with Keytruda cohorts – Mid-2022

INBRX-105**

Oncology

PD-L1 x 4-1BB
Tetravalent Conditional Agonist

• Initial Data-

◦ Escalation with Keytruda cohorts – Q4 2021

◦ Expansion with Keytruda cohorts – Q3 2022

INBRX-101***

Orphan/Respiratory

Neutrophil Elastase
AAT-Fusion Protein

• Initial multiple ascending dose data – Q4 2021

__________________

* Third party partnership with Chinese biotechnology company, Transcenta Holding, Ltd. (formerly Hangzhou Just Biotherapeutics Co., Ltd.), or Transcenta, currently in place for development and commercialization in China, Hong Kong, Macau and/or Taiwan.

** Third party partnership with Chinese biotechnology company, Elpiscience Biopharmaceuticals, Inc., or Elpiscience, currently in place for development and commercialization in China, Hong Kong, Macau and/or Taiwan.

*** Commercialization and development rights outside of the United States and Canada, subject to an option agreement with Chiesi Farmaceutici S.p.A., or Chiesi.

^ The FDA granted fast track designation to INBRX-109 for the treatment of patients with unresectable or metastatic conventional chondrosarcoma in January 2021. Advancing INBRX-109 into registration-enabling randomized Phase 2 trials is contingent upon the FDA’s approval of the Company’s IND amendment, which is planned to be submitted in March 2021.

INBRX-109

INBRX-109 is a precisely engineered tetravalent sdAb-based therapeutic candidate that agonizes DR5 to induce tumor selective programmed cell death. The IND for INBRX-109 became effective in August 2018, and we initiated a three-part, Phase 1 clinical trial in the United States in November 2018. Part 1, the traditional single agent 3+3 dose escalation portion of this trial, was completed in August 2019, with enrollment of 20 patients. INBRX-109 was well-tolerated, with no significant toxicities observed at doses up to and including the maximum administered dose of 30 mg/kg. No maximum tolerated dose, or MTD, was reached.

In September 2019, we commenced Part 2 of this trial with single agent dose expansion cohorts, enrollment of which is still ongoing. During the fourth quarter of 2020, we initiated Part 3, chemotherapy combination cohorts, in malignant pleural mesothelioma and pancreatic adenocarcinoma. Initial data from the combination dose escalation cohorts are expected in the fourth quarter of 2021. As of February 2, 2021, we have enrolled over 104 patients in Part 1 and in the following cancer type specific cohorts: colorectal, gastric and pancreatic adenocarcinomas, malignant pleural mesothelioma, chondrosarcoma and synovial sarcoma.

In January 2021, the FDA granted fast track designation to INBRX-109 for the treatment of patients with unresectable or metastatic conventional chondrosarcoma, which is a serious, life-threatening medical condition with no currently approved effective systemic therapy options. We plan to initiate a registration-enabling Phase 2 trial with progression free survival as the primary endpoint in mid-2021.

We plan to investigate the therapeutic utility of INBRX-109 through a broad clinical development plan across difficult-to-treat cancers. Future clinical development of INBRX-109 may include combinations with additional chemotherapies and potentially synergistic agents in multiple solid tumors and hematologic malignancies. We are currently conducting preclinical studies with INBRX-109 and various rational combination agents, including targeted therapeutics and apoptotic pathway modulators, aimed at guiding our future clinical plans.

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INBRX-106

INBRX-106 is a precisely engineered hexavalent sdAb-based therapeutic candidate targeting OX40 that has the potential to treat numerous cancer indications, both as a single agent and in combination. OX40, also known as TNFRSF4, is a member of the tumor necrosis factor receptor superfamily, or TNFRSF, and is predominately expressed on activated T-cells. Signaling through OX40 provides co-stimulation that promotes T-cell expansion, enhanced effector function and memory cell formation, and prevents activation induced cell death. Based on the capacity for OX40 signaling to enhance anti-tumor immunity in preclinical studies, there have been many efforts to therapeutically exploit this pathway for cancer immunotherapy.

To date, OX40 agonism has mainly been clinically explored with bivalent antibodies. We believe the lack of success with many of these prior attempts resulted from insufficient valency to achieve receptor clustering. We believe INBRX-106, a hexavalent therapeutic candidate with the ability to bind six OX40 molecules per molecule of drug, has the potential to achieve improved receptor clustering and downstream signaling. In preclinical studies, we have observed that INBRX-106 mediated T-cell co-stimulation and also reduced the suppressive activity of regulatory T-cells, with superior activity to bivalent comparators.

The IND for INBRX-106 became effective in June 2019, and we initiated a four-part Phase 1 clinical trial in the United States in December 2019. Part 1 of this trial, single agent dose escalation, was completed in January 2021 with enrollment of 20 patients. INBRX-106 was well-tolerated, without reaching an MTD up to the maximum administered dose of 3 mg/kg.

Part 2 of this trial, single-agent dose expansion, and Part 3 of this trial, dose escalation in combination with Keytruda, were both initiated in February 2021. Initial data from the combination dose escalation cohort of this trial is expected to be announced during the third quarter of 2021. We expect to initiate Part 4 of this trial, the combination expansion cohorts, upon the completion of Part 3 of this trial and to announce initial data from those combination expansion cohorts during the middle of 2022.

INBRX-105

INBRX-105 is a precisely engineered multi-specific sdAb-based therapeutic candidate that is designed to agonize 4-1BB selectively in the presence of PD-L1, which is typically found in the tumor microenvironment and associated lymphoid tissues. We believe that the unique format of INBRX-105, comprised of two PD-L1 targeting domains, each arranged adjacent to a 4-1BB targeting domain, will result in a selective PD-L1 targeted 4-1BB agonist. Based on the enrichment of PD-L1 expression in the tumor microenvironment, we believe INBRX-105 has the potential to selectively activate 4-1BB + T-cells in the tumor microenvironment, thus potentially overcoming the toxicity issues that have limited the success of prior 4-1BB agonists. PD-L1 is a validated biomarker for tumors with the potential for anti-tumor immune activation and thus we believe represents an ideal anchor antigen to drive 4-1BB agonism.

We initiated a four-part Phase 1 clinical trial in February 2019. Part 1, single-agent dose escalation, was completed with enrollment of 32 patients. Part 2, single-agent expansion, was initiated during the first quarter of 2021 and we expect to initiate Part 3 of this trial, escalation in combination with Keytruda, during the second quarter of 2021. We expect to announce initial data from Part 3 of this trial during the fourth quarter of 2021 and Part 4 of this trial, Keytruda combination expansion cohorts, during the third quarter of 2022.

INBRX-101

INBRX-101 is a precisely engineered recombinant human AAT-Fc fusion protein therapeutic candidate, in development for the treatment of AATD. The current standard of care for patients with AATD has been unchanged for decades and relies on weekly infusions of plasma derived AAT, or pdAAT, therapeutics. In spite of the frequent dosing, this therapy is incapable of maintaining serum AAT levels in the normal range for individuals affected by the disease.

Combining proprietary protein engineering with robust process development in INBRX-101, we are seeking to overcome the previous challenge in this field of maintaining the function of recombinant AAT, while manufacturing at commercial scale. We believe INBRX-101 has the potential to be dosed every three weeks, while maintaining patients in the normal range of AAT exposure. This would be a significant improvement for patients, currently receiving weekly infusions and sub-optimal augmentation.

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The IND for INBRX-101 became effective in November 2018, and we initiated a Phase 1 dose escalation clinical trial in July 2019. As a result of the COVID-19 pandemic, we temporarily suspended enrollment for this trial but resumed recruitment during the fourth quarter of 2020. This temporary suspension was not a result of an observation of adverse events and was solely related to circumstances relating to the COVID-19 pandemic. Assuming enrollment continues as we currently anticipate, we expect to complete the multi-dose cohorts during the fourth quarter of 2021.

In May 2019, we entered into an option agreement, as amended in August 2019, or the Chiesi Option Agreement, with Chiesi, pursuant to which we granted Chiesi an exclusive option to obtain an exclusive license to develop and commercialize INBRX-101 outside of the United States and Canada following completion of the Phase 1 trial.

Our Leadership Team

We have assembled a team with deep scientific and clinical experience in discovering and developing protein therapeutics. Our in-house capabilities span the disciplines of discovery, protein engineering, cell biology, translational research, chemistry, manufacturing and controls, or CMC, and clinical development. Members of our team bring experience from multiple organizations including Genentech, Inc., Gilead Sciences, Inc., Merck & Co. and Novartis AG. Our board of directors is comprised of individuals with proven business and scientific accomplishments and significant operating knowledge of our company.

Our Strategy

Our mission is to discover and develop effective biologic treatments for people with life-threatening conditions and to evolve Inhibrx into a commercial-stage biotechnology company with a differentiated and sustainable product portfolio by focusing on the following:

Rapidly advance and optimize the clinical development of our lead programs.

We are focused on rapidly advancing our four therapeutic candidates, each with key clinical data readouts expected in 2021 and 2022. To augment our U.S.-centric clinical strategy for our oncology therapeutic candidates, we have formed collaborations in China designed to provide access to patient populations for clinical trials not readily available in the United States, including treatment-naïve patients, and to facilitate rapid patient enrollment with the goal of generating more robust early clinical data. We believe this harmonized clinical strategy may allow us to accelerate our development timelines. In addition, for each of our therapeutic candidates, should single agent efficacy be demonstrated, we plan to maximize the potential benefit to patients by broadly exploring combinations with standard of care agents and other rational combination agents.

Apply our sdAb platform and other protein technologies to create differentiated therapeutics in focused disease areas with particular emphasis on oncology.

We have developed an sdAb platform and other protein technologies that we believe can be applied to meet the specific challenges of complex target biology. Our current pipeline is focused on oncology and orphan diseases. We plan to focus our internal clinical development where we believe we can create solutions to address the challenges of both validated and novel targets and generate differentiated therapeutics that can be advanced efficiently through clinical development.

Maintain our culture of innovation, execution and efficiency.

Over the last 11 years we have successfully built an innovative culture that encourages scientific risk-taking within the bounds of our data-driven philosophy. This enables our research and development team to discover numerous promising preclinical candidates cost effectively, from which we select what we believe are highly differentiated programs for clinical development.

Maximize the potential of our therapeutic pipeline by retaining rights as well as selectively entering into additional strategic partnerships depending on the therapeutic candidate, indication and geography.

We have a disciplined strategy to maximize the potential of our therapeutic pipeline by retaining development and commercialization rights to those therapeutic candidates, indications and geographies that we believe we can develop and eventually commercialize successfully and efficiently on our own if they are approved, while also seeking to enter into additional strategic partnerships where we believe partnering will accelerate our development timelines and/or maximize the worldwide commercial potential of any approved therapeutic candidates. For

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example, we have granted Chiesi an exclusive option to obtain an exclusive license to develop and commercialize INBRX-101 outside of the United States and Canada following completion of the Phase 1 trial. In addition, we are currently party to license agreements for the development and, if approved, commercialization of INBRX-105, INBRX-106 and INBRX-109 solely in China, Hong Kong, Macau and Taiwan. We otherwise possess the worldwide rights to these candidates. Where appropriate, we plan to seek to enter into additional strategic partnerships with the goal of maximizing the potential of our therapeutic pipeline.

Selectively enter into additional strategic partnerships to maximize the potential of our protein engineering technologies in non-core areas or indications ancillary to oncology.

We believe that the broad potential of our protein engineering technologies, coupled with our strong intellectual property portfolio, can lead to the generation of multiple additional novel product candidates addressing a wide range of therapeutic areas. For example, we licensed our sdAb technologies for specific binders to bluebird bio, Inc., or bluebird, for use in cell therapy. Moreover, we have several preclinical programs focused on non-oncology indications that we are actively seeking to license. Where appropriate, we plan to continue to seek to opportunistically enter into additional strategic partnerships in areas that are considered non-core or indications ancillary to oncology to maximize the potential of our technology platform.

Our Approach

With the goal of addressing unmet medical needs, we leverage our deep understanding of target biology and innovative protein engineering technologies to create therapeutic candidates with attributes and mechanisms of action that are superior to current approaches and applicable to a range of challenging, validated targets with high potential.

Our proprietary sdAb platform allows us to address complex target biology where other biologic approaches have failed or are sub-optimal. Our precision engineering enables the generation of therapeutic candidates with defined valencies and specificities, which we believe can result in optimal mechanisms of action. Initially, we have focused on applying these technologies to targets with clinically validated mechanistic rationales but where prior approaches have lacked sufficient therapeutic activity or safety.

Our clinical pipeline is enabled by our protein and process engineering capabilities, and includes therapeutic candidates in the following categories:

•INBRX-109 and INBRX-106 utilize our multivalent formats, for which the precise valency was optimized in a target-centric way to mediate what we believe to be the most appropriate agonist function;

•INBRX-105’s mechanism of action is enabled by a multi-specific format that we believe enables PD-L1 targeted 4-1BB agonism; and

•INBRX-101 seeks to maintain the natural function of AAT in a recombinant format, optimized for less frequent dosing and greater potential therapeutic activity as compared to pdAAT.

Conventional Antibodies and Their Limitations

Antibodies are multifunctional, Y-shaped proteins, made up of a pair of interacting heavy and light chains to form a symmetric, dimeric molecule with 4 total protein chains. Each arm of the antibody contains an antigen binding region (also referred to as the variable fragment, or Fv), which consists of both a heavy and light variable domain, or VH and VL, respectively, held together through interaction of constant domains. The Fc portion of the heavy-chain constant domain extends the half-life of the antibody in circulation and has the potential to modulate the function of immune cells through interaction with various Fc receptors found on the surface of cells of the immune system.

We believe that antibody Fv domains are not optimal building blocks for multispecific and multivalent therapeutics due to the extensive protein engineering required to ensure the correct pairing of the appropriate VH and VL domains to construct functional Fvs.

One common approach used to achieve correct pairing is the production of single chain variable fragments, or scFvs, which are generated by combining the VH and VL domain antigen binding domains using a flexible linker. Despite the addition of this linker, VH or VL sequences within an scFv have the propensity to errantly pair with a neighboring scFv, and can lead to disruption of proper Fv formation or aggregation. This issue can be exacerbated in

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constructs that contain multiple scFvs, with each entity requiring significant up-front optimization. These formatting challenges may restrict broad applicability of this technology.

To address these limitations, we have developed our sdAb platform to enable the streamlined production of protein formats with multiple antigen specificities. sdAbs are conceptually similar to the VH domain of a conventional antibody but do not contain nor require a paired VL domain, as shown in the image below. Denoted as heavy-chain only antibodies, sdAbs are half the molecular weight of an ScFv, but maintain specific target binding with an affinity range that is comparable to those achieved by conventional antibodies. sdAbs are derived from heavy-chain only antibodies that are naturally produced by animals in the camelid family, which includes camels, alpacas and llamas. Unlike the antibody systems of other mammals, a subset of the camelid antibody repertoire is composed of heavy-chain only antibodies that can be miniaturized into sdAbs. Modular in nature, they can be linked to a constant domain to capture half-life extending and immune cell modulating function. We believe that the small size of sdAbs, along with their stable nature and simple structure, make them ideal building blocks to construct novel biologics with multiple specificities and functions.

Comparison of Conventional Antibody and Single Domain Antibody Structure

Overview of Our sdAb Platform Technology

sdAbs provide a small, simple, modular target binding domain that can be combined in a variety of ways to meet the unique needs of each biological target. We have deep domain expertise surrounding discovery, humanization and optimization of sdAbs and their incorporation into unique configurations enabling the generation of therapeutic candidates with favorable drug-like properties and differentiated mechanisms of action. We have created various multivalent and multispecific therapeutic formats that are each designed to achieve unique functions specifically tailored to the requirements of a given biological target, including the ability to:

•effectively cluster receptors with precisely defined valency;

•simultaneously engage multiple antigens or epitopes;

•combine synergistic functions in a single molecule; and

•restrict therapeutic activity to specific micro environments in the body.

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While the benefits of sdAb proteins are well documented, the presence of pre-existing anti-drug antibodies in human serum may limit the broad use of these agents as therapeutics. We have developed a series of patented modifications to our humanized sdAb scaffold that are designed to eliminate recognition by these pre-existing anti-drug antibodies, without compromising affinity, specificity or stability of the sdAb. We believe this improvement, combined with our extensive knowledge of the structural nuances of sdAbs, will enable the streamlined development of therapeutic candidates with favorable biophysical properties, and will greatly extend the utility and applicability of our sdAb platform. Through our experience, we have found that our sdAb-based therapeutic candidates can be readily manufactured at high yields with established processes used to produce therapeutic proteins.

Overview of Our Multivalent Agonists

Cell surface receptors often require clustering to induce activation and effect downstream signaling. Receptors that require clustering are inherently difficult targets for conventional bivalent therapeutic antibodies, which are limited to interaction with no more than two receptors per molecule. In preclinical studies, we and third parties have observed that increased valency enhances receptor clustering and achieves the desired agonism of specific targets. Our sdAb platform enables us to build therapeutic candidates with a defined number of binding domains, customized to the valency requirements of a given target. We believe this precise protein engineering will increase the potential to achieve optimal clinical benefit by appropriately engaging these clustering-dependent receptors. Using our sdAb platform, we have developed higher order, multivalent antibodies that target TNFRSF agonists, as described below, that contain four (tetravalent) or six (hexavalent) antigen binding domains. Our multivalent therapeutic candidates are generally smaller than conventional antibodies and other multivalent formats that utilize fusions of natural ligands or immunoglobulin M-based, or IgM-based, constant regions, which we believe may confer advantages in the clinic.

INBRX-109

INBRX-109 is a precisely engineered tetravalent sdAb-based therapeutic candidate targeting DR5. DR5 activation induces cancer-specific programmed cell death. The valency of INBRX-109 was selected to maximize the therapeutic index. In patients treated with INBRX-109 to date in our Phase 1 clinical trial, we have observed signs of single agent activity in serious, life-threatening medical conditions that have limited treatment options. In particular, there are no FDA-approved systemic therapies for unresectable or metastatic conventional chondrosarcoma. In addition to the development of INBRX-109 as a single agent, we have initiated cohorts with INBRX-109 in combination with chemotherapies in two solid tumor indications. We continue to conduct preclinical studies with INBRX-109 in combination with various rational combination agents, including targeted therapeutics and apoptotic pathway modulators, aimed at guiding these future clinical plans.

Background on DR5

Apoptosis is a critical process for maintaining healthy tissue homeostasis, but this process is frequently altered in cancer patients leading to the accumulation of malignant cells. Apoptotic signaling pathways are tightly regulated by the balance of pro- and anti-apoptotic factors, and their therapeutic modulation has the potential to be exploited for the treatment of cancer. Targeting anti-apoptotic proteins has been a clinically successful strategy. For example, Venetoclax, an inhibitor of B-cell lymphoma 2, or Bcl-2, was approved by the FDA for the treatment of chronic lymphocytic leukemia in 2016.

Alternatively, we believe therapeutically targeting pro-apoptotic proteins such as DR5, a TNFRSF member, also known as tumor necrosis factor-related apoptosis-inducing ligand, or TRAIL, receptor 2, is a promising oncology treatment strategy. DR5 signaling is induced by clustering of multiple receptors, which initiates an apoptotic signaling pathway resulting in cell death. The strength of apoptotic signaling is proportional to the degree of DR5 clustering. Importantly, although DR5 is expressed throughout the body, cancer cells have been shown to be more sensitive to DR5 signaling compared to healthy cells of normal tissues.

The promise of inducing cancer-specific cell death has led to extensive efforts by pharmaceutical and biotechnology companies to therapeutically exploit the DR5 pathway for the treatment of cancer. These initial efforts centered around developing recombinant versions of the DR5 ligand, TRAIL, and agonistic bivalent DR5 antibodies. Despite demonstrated clinical safety as single agents and in combination with chemotherapies, these first generation DR5

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agonists failed to meet clinical efficacy endpoints. We believe these failures were caused by insufficient clustering of DR5, which is necessary for activation of this pathway.

The prospect of improved efficacy through enhanced DR5 clustering led to the development by a third party of TAS266, a tetravalent DR5 agonist comprised of four DR5 binding sdAbs. This therapeutic candidate showed significantly more potency as compared to the previous generations of DR5 agonists. TAS266 was evaluated preclinically in over 600 human cancer cell lines and demonstrated the greatest activity for mesothelioma, gastric cancer, colorectal cancer, pancreatic cancer and non-small cell lung cancer. Despite these preclinical data, an initial clinical trial indicated that TAS266 caused dose-limiting liver toxicity, or hepatotoxicity. Subsequent analysis suggested pre-existing anti-sdAb antibodies, or PE-ADAs, to TAS266 led to the hyper-clustering of TAS266, adversely increasing the effective valency of the drug candidate and causing apoptosis of liver cells. These findings highlight the importance of tightly controlling valency when developing a drug candidate against this high potential oncology target.

Our Solution - INBRX-109

INBRX-109 is a tetravalent agonist of DR5 that we designed with our sdAb platform to drive cancer-selective programmed cell death and to maximize potency while minimizing on-target liver toxicity arising from hepatocyte apoptosis. We believe INBRX-109 has the potential to overcome the limitations of previous DR5 agonists. As shown in the diagram below, INBRX-109 is comprised of four DR5 targeted sdAbs fused to an Fc region that has been modified to prevent Fc receptor interactions. In preclinical studies, we have observed that INBRX-109 has the ability to potently agonize DR5 through efficient receptor clustering, causing cancer cell death. Based upon the observation that TAS266 induced hepatotoxicity in a Phase 1 clinical trial, hepatocytes appear to be a non-cancerous cell type particularly sensitive to DR5 agonism. We have engineered INBRX-109 with our proprietary sdAb modifications to reduce recognition by pre-existing anti-drug antibodies in humans, which can lessen the potential for hyper-clustering.

INBRX-109: Tetravalent DR5 Agonistic Antibody

We measured the ability of INBRX-109 to kill cancer cells at various antibody concentrations, and compared INBRX-109 to other DR5 binding test articles including a bivalent DR5 antibody and a trivalent TRAIL protein. The figure below shows the viability of the human chondrosarcoma cell line, H-EMC-SS, on the vertical Y-axis, and

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a range of test article concentration on the horizontal X-axis in nanomolar, or nM, units. This assay was used to measure whether these test articles kill cancer cells by reducing the viability from approximately 100% down toward 0%, and also to measure the minimal concentration of test article needed to kill these cancer cells. We observed that only test articles that bound three or more DR5 molecules killed this cancer cell line, while the bivalent conventional antibody did not have any effect. Additionally, we found that the tetravalent DR5 agonist, INBRX‑109, killed H-EMC-SS cells at concentrations over 100 times lower than trivalent TRAIL. Our preclinical data and early clinical data indicate INBRX‑109 may be substantially more potent than recombinant TRAIL or conventional DR5 antibodies previously studied in clinical trials.

Impact of Valency on DR5 Induced Tumor Cell Death

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The anti-tumor activity of INBRX-109 was further assessed in multiple in vivo xenograft models using primary patient-derived, or PDX, tumors or cancer cell lines. In these models, immunodeficient mice were engrafted with either human primary tumor cells or the tumor cell lines. For example, mice bearing tumors of Colo-205 were treated with different doses of INBRX-109 when their tumors reached an average size of about 300 mm3. As shown in the image below, we observed that tumor volume was reduced in mice treated with a single dose of INBRX-109 as low as 0.1mg/kg, administered intravenously, as compared to vehicle-treated mice. Additionally, mice bearing tumors of chondrosarcoma PDX were treated intravenously with 1 mg/kg of INBRX-109 when their tumors reached an average size of about 220 mm3. As shown in the second image below, we observed that tumor volume was reduced in mice treated with three doses of INBRX-109.

Colo-205 Dose Response

The observed clinical hepatotoxicity of hyper-clustered TAS266 highlights the importance of valency toward the therapeutic index of DR5 agonism. We developed an in vitro human hepatocyte assay, that enables us to compare constructs of different valencies and the impact of PE-ADA recognition on hepatocyte viability. Shown below as percentage viability, in this assay, a hexavalent construct, Hex-1F5, composed of six DR5 binding domains, was found to mediate significant hepatocyte death. Additionally, an analog of TAS266 caused the death of human hepatocytes in the presence of pooled immunoglobulins known to contain PE‑ADAs, that recognize single domain antibodies, while meaningful hepatocyte death with INBRX-109 was not observed. We believe that the hepatocyte death mediated by TAS266 observed in this assay was due to hyper-clustering of TAS266 by the PE-ADAs and resulted in an increase in the functional valency. Furthermore, the finding of hepatocyte cell death with the hexavalent DR5 agonist represents a collapsing of the therapeutic index as compared to a tetravalent agonist. We

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believe our assay provides meaningful evidence of an upper bound of the optimal valency and that a tetravalent agonist with reduced recognition by PE-ADAs is the preferred therapeutic strategy for exploiting the DR5 pathway.

Human Hepatocyte Toxicity Assay

Additionally, we observed that INBRX-109 did not induce toxicities in cynomolgus monkeys after up to five weekly INBRX-109 administrations of doses up to 100 mg/kg.

Unmet Medical Need

We are currently investigating INBRX-109 in chondrosarcoma, synovial sarcoma, malignant pleural mesothelioma, and gastric and pancreatic adenocarcinomas. These are some of the most aggressive diseases, certain of which are also orphan oncology indications, that showed signs of activity in preclinical studies. These indications and many of these cancer subtypes do not respond well to currently approved immunotherapies and represent a significant unmet need.

Chondrosarcoma

Chondrosarcoma is a rare malignant bone tumor composed of cartilage matrix-producing cells. It is reported to be the second most common primary bone sarcoma with an incidence of 1 in 200,000 per year globally. The incidence in the United States is reported to be about 1,400 cases per year. There is currently no approved systemic treatment for patients with unresectable or metastatic disease. The placebo arm of a placebo-controlled trial, which tested the hedgehog pathway inhibitor IPI-926 in this indication had a progression free survival of approximately three months. In this trial, IPI-926 did not result in any partial responses and only a small subset of patients had minor reductions in their tumor size.

Malignant Pleural Mesothelioma

Mesothelioma is a malignant tumor most often caused by inhaled asbestos fibers which accumulate in the lining of the lungs, abdomen or heart. The epithelioid subtype is the most common histology of malignant pleural mesothelioma, reportedly comprising about 70% of all cases. It is estimated that as many as 43,000 people worldwide die from mesothelioma each year. There are currently limited approved therapeutic treatments. The placebo arm of a recent large double-blind, placebo-controlled trial testing tremelimumab, an anti-CTLA-4 antibody

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(DETERMINE trial), in malignant pleural or peritoneal mesothelioma with second and third-line patients had a progression free survival rate of 2.7 months and an overall survival rate of 7.3 months. In this trial, tremelimumab did not significantly prolong progression free survival or overall survival compared with placebo in patients with previously treated malignant mesothelioma.

Synovial Sarcoma

Synovial sarcoma is a cancer that can arise from different types of soft tissue, such as muscle or ligaments. It is often found in the arm, leg, or foot and near joints such as the wrist or ankle. It can also form in soft tissues in the lung or abdomen. It is estimated that one to three people per 1,000,000 people are diagnosed with synovial sarcoma each year. Current therapeutic treatments available for unresectable or metastatic synovial sarcoma are doxorubicin or ifosfamide. Pazopanib and trabectedin have also shown activity.

Pancreatic Adenocarcinoma

Pancreatic cancer is a malignant tumor that originates in the pancreas and quickly metastasizes. The most common type of pancreatic cancer, comprising over 90% of all cases, begins in the cells that line the ducts that carry digestive enzymes out of the pancreas, or pancreatic adenocarcinoma. It is estimated that pancreatic cancer accounts for about 3% of all cancers in the U.S. and about 7% of all cancer deaths. Unresectable or metastatic pancreatic adenocarcinoma is often treated with fluorouracil, or 5FU, irinotecan and oxaliplatin, or gemcitabine and albumin-bound paclitaxel chemotherapies, with generally short-lived benefit.

Gastric Adenocarcinoma

Gastric cancer is the second most common cancer worldwide. Greater than 50% of patients present with unresectable locally advanced or metastatic gastric adenocarcinoma. Standard protocols include fluorouracil or capecitabine and oxaliplatin with or without nivolumab, fluorouracil or capecitabine and cisplatin, or other combinations containing irinotecan, paclitaxel, carboplatin, docetaxel, and trastuzumab for HER2 positive gastric adenocarcinoma.

Clinical Data

The IND for INBRX-109 became effective in August 2018, and we initiated a Phase 1 clinical trial in the United States in November 2018. This Phase 1 clinical trial is designed as an open-label, three-part trial in patients with locally advanced or metastatic solid tumors.

Phase 1 INBRX-109 Trial Design and Status

First in human Phase 1 trial started November 2018

Part 1:
Dose Escalation

⇨

⇨

Part 2:
Dose Expansion Cohorts

⇨

⇨

Part 3:
Combination Studies

Completed August 2019

Ongoing

Initiated

Dose Range:

0.3 to 30 mg/kg

N= 20

Result:

Maximum tolerated

dose not reached

N=32

N=10

N=20

N=20

N=10

Chondrosarcoma

Synovial sarcoma

Malignant pleural mesothelioma

Colorectal adenocarcinoma

Gastric adenocarcinoma

N=20

N=20

Pancreatic adenocarcinoma 2nd line with FOLFIRI

Mesothelioma with Cisplatin/Carboplatin
or
Cisplatin/Carboplatin & Pemetrexed

Part 1

Part 1 of the trial utilized a traditional 3+3 dose escalation design escalating INBRX-109 as a single agent from 0.3 mg/kg to 30 mg/kg. Twenty patients were enrolled in this portion of the trial, which was completed in August 2019. INBRX-109 was observed to be well-tolerated without significant toxicities observed at doses up to and including the maximum administered dose of 30 mg/kg. No MTD was reached.

Part 2

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In September 2019, we commenced Part 2 of this trial with single agent dose expansion cohorts, enrollment of which is still ongoing. As of February 2, 2021, we have enrolled over 104 patients in single agent dose cohorts in the following tumor types: colorectal and gastric adenocarcinomas, malignant pleural mesothelioma, chondrosarcoma and synovial sarcoma. We expect to announce initial data from the synovial sarcoma cohort during the second half of 2021.

Part 3

During the fourth quarter of 2020, we initiated chemotherapy combination cohorts in malignant pleural mesothelioma and pancreatic adenocarcinoma. We expect to announce initial data from these combination cohorts during the fourth quarter of 2021.

Primary objectives of the Phase 1 trial are safety, tolerability, and determination of the MTD and recommended Phase 2 dose. Secondary objectives are serum exposure and immunogenicity, as measured by frequency of anti-drug antibodies. Exploratory objectives include clinical anti-tumor efficacy, based on response rate, duration of response, disease control rate, progression-free survival and overall survival, as well as evaluation of potential predictive diagnostic and pharmacodynamic biomarkers.

INBRX-109 Chondrosarcoma

Based on initial data from the chondrosarcoma cohort of our Phase 1 trial, stable disease or partial responses were observed in 9 out of 12 patients with chondrosarcoma, with six of these patients still on treatment as of October 30, 2020. Per investigator requests, an additional 10 patient enrollment slots were added to the chondrosarcoma cohort of the ongoing trial, which were filled as of January 2021. We plan to provide a more mature data set from the chondrosarcoma cohort during the second half of 2021, which will include data on conventional and non-conventional chondrosarcoma patients.

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The CT tumor imaging scan of a chondrosarcoma patient below shows a target lesion, at baseline and at tumor assessment after eight cycles of INBRX-109. This patient achieved a best response of partial response with 60% shrinkage in the target lesions per RECIST (version 1.1).

In January 2021, the FDA granted fast track designation to INBRX-109 for the treatment of patients with unresectable or metastatic conventional chondrosarcoma. We plan to submit an IND amendment for INBRX-109 during the first quarter of 2021. We plan to initiate a registration-enabling Phase 2 trial, with progression free survival as the endpoint, in mid-2021.

Planned Phase 2 Trial Design

Randomized, Blinded, Placebo-controlled, Phase 2 Study of INBRX-109 in Unresectable or Metastatic Conventional Chondrosarcoma

Randomization 2:1

Key eligibility criteria:

• Conventional chondrosarcoma

• Grade 2 and 3

• Unresectable or metastatic

Stratification by histologic grade and line of therapy

⇨

⇨

Until progressive disease (PD) or toxicity

with cross-over

Including

interim futility analysis

• Primary Endpoint:

progression free survival (PFS)

• Secondary Endpoints:

overall survival (OS), overall response rate (ORR)/duration of response (DOR), disease control rate (DCR), quality of life (QoL)

INBRX-109
(2)

Placebo
(1)

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Mesothelioma

In initial data from Part 2 of this trial, we have observed signs of single agent activity in malignant pleural mesothelioma, epithelioid subtype. As of November 24, 2020, time on treatment with INBRX-109 was equal to or greater than 24 weeks in seven of the 19 patients evaluable for response (~37%).

Phase 1 Safety Data

As of February 2, 2021, and based on preliminary Phase 1 data, INBRX-109 has been generally well tolerated in the majority of patients. The chart below is based on 92 patients with available adverse event data and details the adverse events, or AEs, related to INBRX-109 per Investigator assessments. There has been a low incidence of Grade 1, 2, and 3 AEs. Few serious adverse events, or SAEs (including one Grade 5 liver failure and death), and one dose-limiting toxicity, or DLT, were observed.

While the majority of the liver-related AE (e.g., AST increased and/or ALT increased) have been Grade 1 & 2, four patients developed ≥ Grade 3 AE (n=4/92, 4.3%) related to INBRX-109. The first patient, who had an alanine transaminase, or ALT, increase of Grade 2 at baseline and liver metastases from gastric cancer, experienced Grade 3 aspartate transaminase, or AST, and ALT increases during the first cycle of INBRX-109, which were related to

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INBRX-109 per Investigator assessment. The AST and ALT increases were observed to be partially reversible, with a trend towards baseline before the patient enrolled to hospice for progressive gastric cancer. The second patient, who had pleural mesothelioma, was admitted for acute respiratory failure and sepsis due to pneumonia and was found to have Grade 3 AST and ALT increases, which were related to INBRX-109 per Investigator assessment. The AST and ALT increases were observed to be partially reversible, with a trend towards baseline before the patient passed away from acute respiratory failure due to pneumonia. The third patient, who had pleural mesothelioma, was found to have Grade 2 AST and Grade 3 ALT increases during the first cycle of INBRX-109. Per Investigator assessment, these increases were related to INBRX-109 but were transient and fully reversible before the patient began the second cycle of INBRX-109.

The single event of Grade 5 acute liver failure, in a pleural mesothelioma patient, was possibly attributed to INBRX-109 per Investigator assessment. Other possible contributing causes for the Grade 5 acute liver failure considered for this patient were hypoxic liver injury, accidental or intentional overdose of acetaminophen-containing pain medications, and treatment with several other potential hepatotoxic medications and their cumulative toxicity. Notably, this patient screened negative for pre-existing anti-drug antibodies against INBRX-109.


AE Term	AE related to INBRX-109 (very likely, probable, possible)
Grade per CTCAEv5.0	Grade 1 & 2 (N)	Grade 3 (N)	All Grade (N)
Fatigue	16	1	17
AST increased	9	2	11
ALT increased	8	3	11
Nausea	7	1	8
Diarrhea	7	0	7
Pyrexia	5	0	5
Abdominal pain	3	1	4
Rash	3	0	3
Decreased appetite	3	0	3
Headache	3	0	3
One death possibly attributed to study drug, acute hepatic failure in patient with mesothelioma (N=1/92,~1%) 9 out of 92 subjects with INBRX-109-related liver-related AE (~ 10%) Data cut point February 2, 2021 Disclaimers: -Total number of subjects: 92 with reported adverse event data, study ongoing - AE reported ≥ 3 times, causality to INBRX-109 per Investigator assessment - Some data preliminary and subject to change (raw, unvalidated, and verification pending) - Excluded data: uncoded AE; missing AE terms; missing causality; missing severity

Future Clinical Development Plans

We plan to investigate the therapeutic utility of INBRX-109 through a broad clinical development plan across difficult-to-treat cancers. Ewing sarcoma is a rare type of cancer that occurs in bones or in the soft tissue around the bones, more commonly found in children. There are an estimated 1,000 cases of Ewing sarcoma in the United States each year. We plan to initiate enrollment in Ewing sarcoma chemotherapy combination cohort during the middle of 2021 and expect to announce initial data from this combination cohort during the first half of 2022.

Other future clinical development of INBRX-109 may include combinations with additional chemotherapies and potentially synergistic agents in several solid tumors, and hematologic malignancies. We are currently conducting preclinical studies with INBRX-109 and various rational combination agents, including targeted therapeutics and apoptotic pathway modulators, aimed at guiding our future clinical plans.

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INBRX-106

INBRX-106 is a precisely engineered hexavalent sdAb-based therapeutic candidate targeting OX40, designed to be an optimized agonist of this co-stimulatory receptor.

Background on OX40

OX40, also known as TNFRSF4, is a member of the TNFRSF; OX40 is predominately expressed and is a key co-stimulatory receptor on activated T-cells. Signaling through OX40 provides co-stimulation that promotes T-cell expansion, enhanced effector function and memory cell formation, and prevents activation-induced cell death. The natural mechanism of OX40 activation is via the interaction with its trimeric ligand, OX40L, which serves to effectively cluster multiple OX40 molecules and facilitate downstream signaling leading to nuclear factor kappa-light-chain-enhancer of activated B cells, or NFkB, activation. Based on the capacity for OX40 signaling to enhance anti-tumor immunity in preclinical studies, there have been many efforts to therapeutically exploit this pathway for cancer immunotherapy. Most previously developed agents were bivalent OX40 agonists; we believe the bivalent configuration is poorly suited for efficient receptor clustering, which is evidenced by the disappointing clinical responses observed for such molecules.

Our Solution - INBRX-106

As shown in the diagram below, INBRX-106 is composed of six OX40 targeting sdAbs and a functional Fc domain. INBRX-106 is designed to bind six OX40 molecules on the cell surface to mediate efficient receptor clustering and downstream signaling. Additionally, INBRX-106 is able to exploit IgG-mediated effector function via the Fc domain. In preclinical studies, we observed that INBRX-106 can mediate T-cell co-stimulation and reduce the suppressive activity of regulatory T-cells.

INBRX-106: Hexavalent OX40 Agonist

Through a series of preclinical studies, we compared the potential agonist activity of INBRX-106 to bivalent OX40 agonist antibodies. In these studies, INBRX-106 elicited superior OX40 agonism when compared to the bivalent antibodies, 1A7 (analog of MOXR-0916) or 1D10 using an OX40 expressing NFkB reporter cell line, wherein clustering of OX40 receptor mediated signaling culminated in luciferase expression as shown below in relative luminescence units, or RLU, on the Y-axis.

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Valency Drives OX40 Agonism

OX40 Agonism: NFKB Reporter Cell Line

To assess the ability of INBRX-106 to provide co-stimulation and modulate T-cell receptor, or TCR, driven T-cell responses, we conducted various in vitro assays using primary human immune cells. Following anti-CD3 mediated TCR activation of T-cells, INBRX-106 mediated co-stimulation in these assays was superior to a bivalent OX40 antibody at enhancing T-cell proliferation and activation. Representative results are shown below wherein CD4 T-cell proliferation (top left) was monitored by flow cytometric measurement of cell division as shown on the Y-axis as % proliferated Interferon gamma, or IFNγ, production (top right) was assessed by ELISA as shown on the Y-axis in pg/ml. CD4 T-cell activation as determined by flow cytometric measurement of CD25 (bottom left) and CD71

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(bottom right) as shown on the Y‑axis as mean fluorescence intensity, or MFI. INBRX-106 was found to mediate similar co-stimulation of CD4 and CD8 T-cells.

Syngeneic tumor models are a commonly used tool to investigate the anti-tumor activity of immunomodulatory agents. INBRX-106, however, does not interact with mouse OX40. Therefore, in order to investigate the potential of an INBRX-106-like mechanism to mediate anti-tumor immunity in a preclinical model, we developed mu106, a molecule that has a matched hexavalent, sdAb-based therapeutic format and binds mouse OX40 with a similar affinity to that of INBRX-106 on human OX40. We tested mu106 in numerous syngeneic tumor models and observed robust single agent anti-tumor activity, as well as enhanced anti-tumor activity in combination with a PD‑1 blocking antibody. As shown below, presented as the individual tumor growth curve of each mouse in a given treatment group (n=10 mice/group), mu106 (Hexavalent OX40 mAb) elicited superior anti-tumor activity compared to a bivalent OX40 antibody or a PD-1 blocking antibody, or a combination thereof. Furthermore, the anti-tumor

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activity of mu106 was enhanced in combination with a PD-1 blocking antibody. It is generally accepted that PD-1/PD-L1 blocking agents display minimal anti-tumor activity in the B16-F10 syngeneic tumor model.

Unmet Medical Need

The approval of immune checkpoint inhibitors that block CTLA-4 or PD-1, or their ligands such as PD-L1 respectively, has caused a paradigm shift in oncology treatment due to their substantial response rates and overall survival benefit across numerous cancers. However, the checkpoint inhibitors achieve lasting benefit or cure only in a subset of patients and therefore, additional therapeutics are required to further stimulate an anti-cancer immune response. We plan to clinically evaluate INBRX-106 as a single agent to reach into tumors not responsive to current checkpoint inhibitor therapy ("cold" tumors) and to combine INBRX-106 synergistically with PD-1 or other checkpoint inhibitors, vaccines, and other immune stimulatory approaches.

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Clinical Data

We initiated a Phase 1 clinical trial in December 2019 for INBRX-106. This Phase 1 trial is designed as an open-label, four-part trial in patients with locally advanced or metastatic solid tumors.

Phase 1 INBRX-106 Trial Design and Status

First in human Phase 1 trial started December 2019

Part 1:
Single Agent
Dose Escalation

⇨

⇨

Part 2:
Single Agent
Dose Expansion

⇨

⇨

Part 3:
Combination
Dose Escalation

⇨

⇨

Part 4:
Combination
Dose Expansion

Completed January 2021

Started February 2021

Planned

Dose Range:

0.0003 to 3 mg/kg

N= 20

Result:

Maximum tolerated

dose not reached

INBRX-106:
RP2D
Two
Dosing
Schedules

N=24

Basket

INBRX-106 + Keytruda

Dose Range:
0.01 to 0.3 mg/kg

Minimum N=12

INBRX-106 + Keytruda

(post PD-1/PD-L1

Checkpoint Inhibitor)

N= 60

PD-L1+ NSCLC (1st cohort)

PD-L1+ NSCLC (2nd cohort)

PD-L1+ basket

Part 1 of the trial utilized a traditional 3+3 algorithm for single agent dose escalation from 0.0003 mg/kg to 3 mg/kg. Twenty patients were enrolled in this portion of the trial, which was completed in January 2021. INBRX-106 was observed to be generally well tolerated in humans, with only three serious adverse events, one Grade 3 AE and one DLT. The most common AEs reported for INBRX-106 were Grade 1 and 2 rashes or dermatitis, cytokine release syndrome, fatigue, and infusion-related reactions. Notably, cutaneous toxicities are common immune-related AEs associated with immune checkpoint inhibitors. These mostly mild or moderate and likely immune-related toxicities were in line with the mechanism of action of this candidate therapeutic. The maximum administered dose was 3 mg/kg and the MTD level was not reached.

Signs of clinical benefit to date were observed in patients with a range of cancer types, including tumors generally considered to be “hot” (a tumor that has been infiltrated by T-cells) and “cold” (a tumor that has not been infiltrated by T-cells), as well as in patients that were relapsed or refractory to checkpoint inhibitors. Activity was observed at dose levels in a range from 0.0003 to 0.3 mg/kg and peripheral biomarker sampling confirmed agonist activity across these low doses. As of March 3, 2021, preliminary single agent data from the first 20 patients treated in the dose escalation portion of this trial, and with available tumor assessment data, demonstrated stable disease for eight patients as shown below. These stable diseases occurred at low dose levels. As of March 3, 2021, the longest duration of stable disease was 50 weeks, or approximately eleven and a half months, and the greatest reduction in tumor volume per RECIST was 23%.

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Phase 1 INBRX-106 Dose Escalation Status

Part 1 as of March 3, 2021

Dose Level
mg/kg

Demographics

Tumor Type

Notable Prior Therapies and Best Response

INBRX-106 Best Response

Notable Time on INBRX-106

0.0003 - 0.003

59 M W

Small intestine cancer (GIST)

S/p 8 lines, no CPI

SD (+2%)

32 weeks

0.001 - 0.01

85 F W

Melanoma (cutaneous)

S/p Pembrolizumab SD ~3.5y

SD (-23%)

40 weeks

0.003 - 0.01

69 M W

Bladder CA

S/p 2 lines, Nivolumab PD 5mo

0.01 - 0.1

56 F O

NSCLC, AD (PD-L1 40%)

S/p Carboplatin/Pemetrexed/Pembrolizumab PD 2mo

SD (Non-measurable)

50 weeks, ongoing

0.03 - 0.1

54 M W

Esophageal AD

0.1

55 M W

Esophageal AD

S/p 4 lines, Pembrolizumab PD 3mo

SD (+12%)

12 weeks

0.1

78 M W

Prostate AD (CRPC)

S/p 6 lines, no CPI

SD (+6%; PSA -52%)

18 weeks

0.1

58 F W

RCC (sarcomatoid features)

0.3

70 F W

Chondrosarcoma

S/p 1 line, Spartalizumab/IL-15/IL-2 12mo SD

SD (+7%)

12 weeks

0.3

71 M W

HNSCC

NE (DLT)

0.3

47 M W

Colon AD (KRAS mutation)

0.3

60 M W

NSCLC, AD (PD-L1 0%)

S/p 6 lines, Nivolumab SD ~3.5y, Atezolizumab/Bevacizumab ~SD 1.5y

SD (-2%)

30 weeks, ongoing

0.3

74 M O

RCC (clear cell)

S/p 2 lines, Nivolumab UK ~3y

SD (+6%)

9 weeks

0.3

80 F W

Breast AD (IDC)

1.0

72 F W

Atypical carcinoid pulmonary

1.0

46 M W

Rectal AD

1.0

71 M W

Pancreatic AD

3.0

55 F W

RCC

3.0

50 F W

Colon AD

iuPD

3.0

65 M W

Pancreatic AD

*Stable disease (SD); Progressive disease (PD); Immune unconfirmed progressive disease (iuPD);Not evaluable (NE); Unknown (UK); Adenocarcinoma (AD); Renal cell carcinoma (RCC); Castration-resistant Prostate Cancer (CRPC); Prostate-specific antigen (PSA); Head and Neck Squamous Cell Carcinoma (HNSCC); Non-small Cell Lung Cancer (NSCLC); Invasive Duct Carcinoma (IDC); Small Cell Lung Cancer (SCLC); Checkpoint Inhibitor (CPI) Male (M); Female (F); White (W); Other (O)

Future Clinical Development Plan

With the conclusion of Part 1of the trial, single agent dose escalation, Part 2 of the trial, single agent dose expansion, was initiated in February 2021. Utilization of extensive biomarker data guided the determination of the optimal dose for Part 2 of the trial, which we believe to be 0.03 mg/kg. Key attributes leading to the choice of this dose level included OX40 occupancy data, evidence of peripheral memory T-cell activation and proliferation, and sufficient drug clearance to allow target recovery prior to the next dose administration. Part 2 treatment cohorts of this trial are in the following tumor types: non-small cell lung cancer, melanoma, head and neck squamous cell carcinoma, gastric or gastro-esophageal junction adenocarcinoma, renal cell carcinoma, and urothelial (transitional) cell carcinoma.

In Parts 3 and 4 of this trial, INBRX-106 will be evaluated in combination with Keytruda, a PD-1 blocking checkpoint inhibitor. In Part 3 of the trial, which initiated in February 2021, INBRX-106 will be escalated in combination with Keytruda. Patients in the INBRX-106 combination expansion cohorts in Part 4 will have non-small cell lung cancer or melanoma, head and neck squamous cell carcinoma, gastric or gastro-esophageal junction adenocarcinoma, renal cell carcinoma, and urothelial (transitional) cell carcinoma, which are positive for PD-L1 expression, as determined by immunohistochemistry and possessing adequate hematologic and organ function, to qualify for enrollment.

We expect the entire trial will be conducted at approximately 10-12 clinical sites in the United States and enroll approximately 120 patients.

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Primary objectives of the trial are safety and tolerability, and the determination of the MTD and recommended Phase 2 dose of INBRX-106 as a single agent, and INBRX-106 in combination with Keytruda. Secondary objectives will be serum exposure, immunogenicity, as measured by frequency of anti-drug antibodies, and clinical anti-tumor efficacy per RECIST (version 1.1) and immune RECIST based on response rate, duration of response, disease control rate, progression-free survival and overall survival. Exploratory objectives will include evaluation of potential predictive diagnostic and pharmacodynamic biomarkers.

We expect to announce initial data from dose escalation in combination with Keytruda during the third quarter of 2021 and dose expansion in combination with Keytruda during the third quarter of 2022.

Overview of Our Conditional Agonists

Our pipeline includes conditional agonist therapeutic candidates designed to restrict functional activity to the specific site where a given antigen is expressed, for example, restricting the co-stimulation of T-cells to the tumor microenvironment. By agonizing receptors that function to promote an anti-tumor immune response in a manner that is dependent on a tumor-biased target, conditional agonists have the potential to induce anti-tumor activity without generating systemic toxicities. Our sdAb platform allows for careful selection of the affinity and valency of targeting domains, which we believe may provide optimal biologic activity and systemic exposure, potentially achieving a superior therapeutic index.

INBRX-105

Background on Immunotherapy and Unmet Medical Need

A notable recent success in cancer treatment is the approval of checkpoint inhibitor immunotherapies as therapeutic agents. Immune checkpoints are key mechanisms that fine-tune and control the body’s immune response. In the cancer setting, tumors have developed strategies for hijacking these checkpoints, preventing an immune response to the cancer and allowing the tumor cells to proliferate unchecked. Checkpoint inhibitor immunotherapies were developed to overcome this phenomenon by relieving immune cell inhibition, resulting in a potentially long-lasting amplification of the anti-tumor immune response. Therapies against checkpoint proteins, such as PD-1 and PD-L1, produced impressive results in clinical development, resulting in regulatory approvals in a number of malignancies.

Despite unprecedented clinical response rates, the majority of patients fail to respond to therapies targeting PD-1 and PD-L1. We believe this is in part because T-cells require co-stimulation for full functionality. Thus, checkpoint inhibition alone is likely insufficient to fully enable the immune system to attack a tumor, and we believe further benefit could be derived by the addition of immune co-stimulatory agents.

We believe a promising co-stimulatory receptor is 4-1BB, also known as TNFRSF9 or cluster of differentiation 137, which has been identified on T-cells isolated from primary tumors. 4-1BB is a member of the TNFRSF and is expressed on recently activated T-cells but is largely absent from circulating T-cells under normal conditions. Agonistic 4-1BB antibodies have exhibited anti-tumor activity in mouse models of cancer, especially in combination with other immunomodulatory or tumor targeted therapeutics. These observations motivated the clinical advancement of antibodies designed to agonize 4-1BB and co-stimulate tumor reactive T-cells. Most recently, urelumab, a 4-1BB agonist, showed initial signs of single agent therapeutic efficacy, but clinical investigation was halted due to dose-limiting liver toxicities. The resulting data suggest there is potential for 4-1BB agonists to exert anti-cancer function, but also suggest a potentially significant safety advantage for therapeutics able to enrich for 4-1BB activation in the tumor microenvironment.

Our Solution - INBRX-105

INBRX-105 is a precisely engineered multi-specific sdAb-based therapeutic candidate that is designed to agonize 4-1BB selectively in the presence of PD-L1, which is typically found in the tumor microenvironment and associated lymphoid tissues. We believe that the unique format of INBRX-105, comprised of two PD-L1 targeting domains, each arranged adjacent to a 4-1BB targeting domain, should result in a best-in-class PD-L1 targeted 4-1BB agonist. Based on the enrichment of PD-L1 expression in the tumor microenvironment, we believe INBRX-105 has the potential to selectively activate 4-1BB + T-cells in the tumor microenvironment, thus overcoming the toxicity issues that have limited the success of prior 4-1BB agonists. PD-L1 is a validated biomarker for tumors with the potential

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for anti-tumor immune activation and thus we believe represents an ideal anchor antigen to drive 4-1BB agonism. The image below illustrates the unique structure of INBRX-105.

INBRX-105: A PD-L1 Targeted 4-1BB Agonist

We tested INBRX-105 in a variety of in vitro assays to evaluate its ability to mediate PD-L1 dependent 4-1BB agonism. In some cases, we compared the 4-1BB agonistic activity to analogs of conventional anti-4-1BB antibodies with published mechanisms and clinical experience, urelumab or utomilumab. The figure below shows the results of a study in which reporter cells expressing 4-1BB on the surface were mixed with a second cell population that either did or did not express PD-L1 on the surface. Activation of 4-1BB receptors through clustering drives signaling and subsequent luciferase expression in the reporter cell line, read as RLUs, and shown on the vertical axis. We observed that INBRX-105 only activated 4-1BB signaling in the presence of PD-L1 expressing cells and had no effect on 4-1BB signaling in the presence of cells lacking PD-L1. Furthermore, these assays revealed that the analog of urelumab was a constitutive agonist of 4-1BB signaling, whereas the analog of utomilumab did not display agonistic activity, demonstrating distinct mechanisms of action among the three therapeutic candidates.

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INBRX-105 PD-L1-Dependent 4-1BB Agonism

To assess the potential ability of INBRX-105 to modulate the activity of T-cells activated through TCR engagement, we conducted various in vitro assays using primary human immune cells. One such assay, an allogeneic mixed lymphocyte reaction, or MLR, is commonly used to evaluate the propensity of immunomodulatory agents to provide T-cell co-stimulation. Therein, T-cells are induced to secrete the cytokine IFNγ, as a result of TCR clustering and activation. This cytokine secretion can be greatly enhanced through concurrent activation of co-stimulatory receptors, such as 4-1BB. In an MLR, we observed superior IFNγ production by INBRX-105, shown on the vertical axis in the figure below, as compared to Keytruda, Tecentriq or the combination of these therapeutics and an analog of the 4‑1BB antibody, utomilumab. We have also observed similar effects in human T-cells stimulated ex vivo with a specific viral antigen to achieve TCR activation.

Mixed Lymphocyte Reaction: IFNγ Production

Syngeneic tumor models are a commonly used tool to investigate the anti-tumor activity of immunomodulatory agents. However, INBRX-105 does not interact with either mouse PD-L1 or 4-1BB. Therefore, in order to investigate the potential to mediate anti-tumor immunity preclinically, we developed a surrogate version of INBRX-105, mu105, with analogous format and function on mouse PD-L1 and 4-1BB. To test the tumor centric activation of 4-1BB, we evaluated the activity of mu105 in the MC38 colorectal carcinoma syngeneic model, as this model is known to express PD-L1 on both tumor and infiltrating immune cells. As shown in the figure below, a 2 mg/kg dose of mu105 activated 4-1BB, as shown by an increase in effector memory T-cells, or Tem cells, as a percentage of total CD8 T-cells. This dose level provided a short duration of 4-1BB agonism, but maintained the

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ability to activate anti-tumor immune cells, as evidenced by the robust tumor control in combination with an anti-PD-1 blocking antibody. We believe that this data demonstrates the potential for 4-1BB agonism through an INBRX-105 like mechanism to meaningfully alter the T-cell population, enrich for cells with anti-tumor capacity, and provide co-stimulation with potential for synergistic activity with an anti-PD-1 check point inhibitor.

Clinical Data

We initiated a Phase 1 clinical trial in the United States in February 2019. This Phase 1 trial is designed as an open-label, four-part trial in patients with locally advanced or metastatic solid tumors and is being conducted at approximately 10-12 clinical sites in the United States.

Phase 1 INBRX-105 Trial Design and Status

First in human Phase 1 trial started February 2019

Part 1:
Single Agent
Dose Escalation

⇨

⇨

Part 2:
Single Agent
Dose Expansion

⇨

⇨

Part 3:
Combination
Dose Escalation

⇨

⇨

Part 4:
Combination
Dose Expansion

Completed

Started Q1 2021

Planned

INBRX-105

N=32

Dose range:
0.001 to 3 mg/kg

INBRX-105

N=32

Dose range: RP2D

PD-L1+ NSCLC
PD-L1+ Melanoma
PD-L1+ Head & Neck Cancer
PD-L1+ Basket

Indications based on known sensitivity to 4-1BB and/or checkpoint blockade

INBRX-105 + Keytruda

Minimum N=9

Dose range: RP2D

Locally advanced or
metastatic solid tumors

INBRX-105 + Keytruda

N= 80

Post PD-1/PD-L1
Checkpoint Inhibitor:
PD-L1+ NSCLC
PD-L1+ Melanoma
PD-L1+ Basket
CPI naive: PD-L1+ NSCLC

Single agent dose escalation was completed with a total of 32 patients enrolled. We observed dose-limiting toxicities, which were consistent with immune related adverse events, such as hepatitis, arthritis and myalgia/hyperthyroidism, at several dose levels and determined the 1 mg/kg dose level as the MTD of INBRX-105. Patients in this part of the study were not pre-screened for PD-L1 expression. Eight out of 18 evaluable patients (44%), who were dosed at the 0.1 mg/kg dose level or above, achieved stable disease, with the greatest reduction in tumor volume observed to be 20% by RECISTv1.1. The longest duration on treatment with INBRX-105 was 41 weeks, or approximately nine and a half months. Notably, seven patients with stable disease tested positive for PD-L1 expression, with a minimum of 1% positivity as determined by immunohistochemistry (Range 1 to 95%), and the

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results of one patient are pending. Four of these eight patients were refractory to or progressed on prior PD-1 checkpoint inhibitors.

Single agent dose expansion began enrolling during the first quarter of 2021. Part 2 of this trial will consist of 32 patients in expansion cohorts in each of non-small cell lung cancer, melanoma, head and neck squamous cell carcinoma, as well as a basket cohort of gastric or gastro-esophageal junction adenocarcinoma, renal cell carcinoma, and urothelial (transitional) cell carcinoma. Patients in the expansion cohorts for Part 2 of this trial will have to be positive for PD-L1 expression, as determined by immunohistochemistry, to qualify for enrollment.

Future Clinical Development Plan

We expect to achieve the maximal therapeutic benefit of INBRX-105 in combination with PD-1 checkpoint blockade. Our preclinical studies demonstrate that acute exposure to PD-L1 dependent 4-1BB agonism is sufficient to derive maximal anti-tumor activity when co-dosed with another PD-1 blocking agent at a target saturating dose. As such, a dose escalation cohort of INBRX-105 in combination with Keytruda is targeted to initiate enrollment during the second quarter of 2021 and we expect to announce initial data during the fourth quarter of 2021.

Part 4 of this trial will consist of combination expansion cohorts in each of non-small cell lung cancer, melanoma, head and neck squamous cell carcinoma, as well as a basket cohort of gastric or gastro-esophageal junction adenocarcinoma, renal cell carcinoma, and urothelial (transitional) cell carcinoma, which are positive for PD-L1 expression and are refractory to or progressed on prior PD-1 checkpoint inhibitors. Additionally, we are planning to evaluate INBRX-105 in combination with Keytruda in checkpoint inhibitor naive non-small cell lung cancer patients that are positive for PD-L1 expression. We expect to announce initial data from the Part 4 combination expansion cohorts during the third quarter of 2022.

Primary objectives of the Phase 1 trial are safety, tolerability, and the determination of the MTD and recommended Phase 2 dose of INBRX-105 and INBRX-105 in combination with Keytruda.

Secondary objectives are serum exposure, immunogenicity, as measured by frequency of anti-drug antibodies. Exploratory objectives include clinical anti-tumor efficacy per RECIST (version 1.1) and immune RECIST based on response rate, duration of response, disease control rate, progression-free survival and overall survival, as well as evaluation of potential predictive diagnostic and pharmacodynamic biomarkers.

Overview of Our Therapeutic Candidate Utilizing Unique Protein Engineering

INBRX-101

INBRX-101 is a precisely engineered recombinant human AAT-Fc fusion protein therapeutic candidate that we are developing for the treatment of patients with AATD. We believe INBRX-101 has the potential to be dosed every three weeks, while maintaining patients in the normal range of AAT exposure, which would be a significant improvement for patients currently receiving weekly infusions. Through our proprietary engineering capabilities, we were able to overcome the challenges of producing AAT recombinantly and manufacturing at commercial scale.

Overview of AATD and Unmet Medical Need

AATD is an inherited disease that causes an increased risk of developing pulmonary disease defined by progressive loss of lung tissue and function and is associated with decreased life expectancy. The pulmonary manifestations of AATD include the entire spectrum of emphysema and disorders associated with chronic obstructive pulmonary disease. Patients with AATD harbor mutations in the AAT-encoding gene Serpin family A member 1 which causes AAT protein misfolding, loss of activity and retention in the liver. AAT is a protease inhibitor that primarily targets human neutrophil elastase, or NE, an enzyme that is released by white blood cells in response to infections and has the capacity to degrade normal tissues, especially in the lung, if not tightly controlled by AAT.

According to the Alpha-1 Foundation, the disease affects roughly 100,000 people in the United States, with a similar number of patients in Europe. Since AATD must be diagnosed using laboratory testing and cannot be diagnosed by symptoms or by a medical examination alone, it is believed that many individuals with AATD are likely undiagnosed or misdiagnosed. In April 2017, the FDA allowed for the marketing of direct-to-consumer tests that

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provide genetic risk information for certain conditions, including AATD. We believe such tests will lead to earlier diagnosis and an increase in the number of patients identified with AATD.

The approved standard of care for AATD has been augmentation therapy using pdAAT and has not been substantially improved since 1987. Plasma-derived treatments are highly dependent on human donor blood supply, which is costly and can be limited. Due to the short half-life of pdAAT therapeutics, patients require weekly infusions to achieve and maintain serum concentration above the protective threshold, presumed to be 11 µM. However, even with frequent treatments, the AAT serum concentration following treatment remains considerably below the normal range of 20 to 50 µM. There is clinical evidence suggesting that maintenance of higher AAT serum trough levels may better protect against lung function decline. The graph below is an adaptation based on published data that depicts the pharmacokinetic profile of pdAAT. The published results from the RAPID trial revealed the correlation of serum AAT through levels and lung density decline in AATD patients. Additionally, there are other significant barriers to treatment for patients with AATD, including under-diagnosis, high cost of chronic augmentation therapy, and difficulties associated with administering intravenous infusions on a weekly basis. It has been reported that the global AATD augmentation therapy market size was valued at $1.1 billion in 2018 and is projected to reach $1.9 billion by the end of 2026.

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Our Solution - INBRX-101

INBRX-101 is a recombinant AAT protein that is comprised of two human AAT molecules covalently linked to the Fc region of human immunoglobulin G4. AAT has proven difficult to develop recombinantly, often displaying loss of activity and experiencing accelerated degradation. We believe our novel approach has the potential to overcome these challenges in our clinical trials. Fusion of AAT to the Fc region allows for production using a standard antibody expression system, which, when combined with our proprietary AAT-function preserving purification process, generates substantial and potentially scalable yields of active recombinant AAT protein. In preclinical studies, we have observed the Fc region to significantly improve pharmacokinetic properties for INBRX-101 as compared to pdAAT therapeutics. Our clinical trials will seek to demonstrate that this extended exposure supports the potential for dosing every three weeks while maintaining patients in the normal range of AAT exposure, which in turn would reduce the frequency of annual infusions and could significantly improve patient quality of life.

In our preclinical studies, we compared INBRX-101 to pdAAT therapeutics across several parameters. INBRX-101 is intended to maximize the functional activity of AAT, particularly in the lung.

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It is known that AAT is inactivated by oxidation, which can occur from the oxidative burst of neutrophils or inhalation of pollutants. Therefore, we designed INBRX-101 with amino acid changes in the AAT sequence to mitigate oxidation-induced inactivation, with the goal of preventing loss of activity at the desired site of action.

The primary mechanism of action of INBRX-101 is to inhibit NE. In a preclinical assay, we measured the ability of INBRX-101 to inhibit NE by comparing INBRX-101 to the FDA-approved pdAAT, Prolastin-C, in the presence of NE and a substrate that becomes florescent when it is cleaved by NE. The vertical Y-axis shows the activity of NE as the rate of relative fluorescence units over time, orRFU/sec, while the X-axis shows the concentration of either INBRX-101 or Prolastin-C. The figure below shows that as the concentration of INBRX-101 or Prolastin-C increases, the RFU/sec decreases indicating that NE is being inhibited by both test articles with equivalent potency.

INBRX-101 vs. Prolastin-C: Neutrophil Elastase Inhibition

The primary pathology of AATD is lung density decline due to NE degradation of elastin in the lung. Therefore, it is critical that INBRX-101 penetrates the physiological site where NE is degrading elastin, which is inside the lung. We performed a lung drug distribution study to measure the concentration of INBRX-101 and Prolastin-C in mice expressing human FcRn treated with either test article. The figure below shows the concentration of both INBRX-101 and Prolastin-C in the broncheoalveolar lavage fluid, or BALF (fluid in the lungs), of hFcRN transgenic mice 48 hours after intravenous treatment, with each circle representing an individually dosed animal.

INBRX-101 vs. Prolastin-C: Lung Exposure huFcRN Tg Mice

Clinical Data

We initiated a Phase 1 clinical trial in July 2019. The Phase 1 trial is an open-label, dose escalating trial and is designed as single ascending dose administrations followed by multiple ascending dose administrations of INBRX-101 with doses of 10 mg/kg, 40 mg/kg, 80 mg/kg or 120 mg/kg, administered to patients diagnosed with

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AATD who are either treatment naïve or previously treated with pdAAT therapeutics. As of July 24, 2020, and based on preliminary Phase 1 safety data in 5 patients, INBRX-101 has been well tolerated in humans, without any significant possibly- or probably-related AEs, and without any SAEs or DLTs.

The graph on the left below depicts the preliminary pharmacokinetic, or PK, profiles for the first five patients dosed with INBRX-101 at a dose of 10 mg/kg, demonstrating an estimated half-life of approximately 13 days. The PK profile of INBRX-101 in humans was observed to be consistent with preclinical findings in cynomolgus monkeys and rats. The graph on the right below depicts the results of a PK model based on preclinical data, to estimate the exposure of INBRX-101 over time when dosed at 120 mg/kg dosed every three weeks (green). This modeling data is overlaid on the published PK profile of pdAAT dosed weekly at the approved 60 mg/kg (blue). Based on this model and the observed consistency between the human PK data collected to date and preclinical studies, we expect that INBRX-101, dosed significantly less frequently than pdAAT, will be able to maintain AAT serum exposure in the normal range.

We expect the trial to be conducted in approximately 12 clinical sites in the United States, the United Kingdom and New Zealand and will enroll approximately 36 patients. Based on preclinical pharmacokinetic data, we have designed the dose escalation trial to administer INBRX-101 by intravenous infusion every three weeks with the intent to select a dosage necessary to achieve sustained, normal, serum levels of AAT within this dosing interval.

Primary endpoints of the trial are safety and tolerability. Secondary endpoints are serum exposure and immunogenicity, as measured by frequency of anti-drug antibodies. Exploratory endpoints include NE activity and its biomarkers. In addition, we will measure pharmacokinetic and pharmacodynamic biomarkers in BALF.

In May 2019, we entered into the Chiesi Option Agreement with Chiesi, pursuant to which we granted Chiesi an option to obtain an exclusive license to develop and commercialize INBRX-101 outside of the United States and Canada following completion of the Phase 1 trial.

As a result of the COVID-19 pandemic, including patient travel restrictions, we temporarily suspended enrollment in this trial but resumed enrollment during the fourth quarter of 2020. The temporary suspension of enrollment was not related to any observed adverse events from our Phase 1 trial or required by any third party or regulatory authority. Rather, this suspension was made at our discretion and was directly related to circumstances involving the COVID-19 pandemic. Assuming enrollment continues as we anticipate it will, we expect to announce initial Phase 1 data from the multi-dose cohorts during the fourth quarter of 2021. Assuming positive data from this trial, we believe we could initiate potential registration-enabling Phase 2 trials in late 2022.

Other sdAb Development Programs

We believe that the breadth of our technological platform and our strong intellectual property portfolio will enable us to generate multiple future clinical candidates representing significant future revenue opportunities. We plan to continue to advance our sdAb platform and other protein technologies in areas that are considered non-core or indications ancillary to oncology via out-licensing agreements and other corporate partnerships.

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License and Collaboration Agreements

We have entered into various license and collaboration agreements. The license agreements discussed below pertain to intellectual property that we own and license to the parties identified below. We retain ownership of the intellectual property subject to the license agreements.

Elpiscience Agreements

We have entered into two different license agreements with Elpiscience Biopharmaceuticals, Inc., or Elpiscience. Each agreement is a standalone license to Elpiscience of a distinct and differentiated protein therapeutic candidate with a separate biological target.

On February 28, 2018, we entered into a license agreement, or the PD-L1 and 4-1BB License Agreement, with Elpiscience, pursuant to which we granted Elpiscience an exclusive license to our bi-specific therapeutic candidate designed to target PD-L1 and 4-1BB, also referred to as INBRX-105. On April 30, 2018, we entered into a license agreement, or the OX40 License Agreement, with Elpiscience, pursuant to which we granted Elpiscience an exclusive license to our multivalent protein therapeutic directed to the biological target OX40, or INBRX-106. Each of the PD-L1 and 4-1BB License Agreement and OX40 License Agreement provides Elpiscience with the right to further advance the respective therapeutic candidates through clinical trials, as well as to manufacture and commercialize these therapeutic candidates in China, Hong Kong, Macau and Taiwan. The PD-L1 and 4-1BB License Agreement and OX40 License Agreement also require us to provide Elpiscience with know-how and materials specific to INBRX-105 and INBRX-106, respectively, including process development and manufacturing data and information necessary to develop INBRX-105 and INBRX-106. Additionally, pursuant to each of the license agreements, Elpiscience granted to us a royalty-free, worldwide, non-exclusive research license to intellectual property created by Elpiscience that incorporates intellectual property we licensed to Elpiscience. In the PD-L1 and 4-1BB License Agreement and OX40 License Agreement, we also agreed to negotiate an agreement to supply Elpiscience with INBRX-105 and INBRX-106, respectively, for their development in China, Hong Kong, Macau and Taiwan.

As payment for the license granted in the PD-L1 and 4-1BB License Agreement, we received a non-refundable upfront payment of $2.5 million and reimbursement of $3.0 million for certain costs we incurred. As payment for the license granted in the OX40 License Agreement, we received a non-refundable fee of $2.5 million, payable in two installments, and reimbursement of $3.4 million for certain toxicology study costs and chemistry, manufacturing and controls costs. In December 2018, we received the first milestone payment of $2.0 million under the PD-L1 and 4-1BB License Agreement. We are also eligible to receive specified developmental and commercial milestone payments of up to an aggregate of $100.0 million under each of the PD-L1 and 4-1BB License Agreement and the OX40 License Agreement. Additionally, we received reimbursement for specific supply-related costs in the amounts of $1.7 million and $1.5 million related to the PD-L1 and 4-1BB License Agreement and the OX40 License Agreement, respectively. Further, each license agreement provides us with the right to receive percentage tiered royalties on future product sales with rates in the high single-digits.

Each of the PD-L1 and 4-1BB License Agreement and the OX40 License Agreement contains representations and warranties, insurance, indemnification and confidentiality provisions customary for similar agreements and arrangements. The terms of the PD-L1 and 4-1BB License Agreement and the OX40 License Agreement commenced on February 28, 2018 and April 30, 2018, respectively, and expire on a country-by-country basis upon the full expiration of Elpiscience’s milestone- and royalty-based payment obligations under each license agreement. The royalty obligations expire upon the later of (i) the expiration of the last valid patent claim for the applicable product in the relevant jurisdiction, and (ii) 12 years following that date of the first commercial sale of the applicable product in the relevant jurisdiction. Each license agreement may be terminated by (i) either party for the uncured material breach of the other party, (ii) either party for bankruptcy or other insolvency proceedings of the other party, and (iii) Elpiscience at any time upon 90 days’ written notice to us. As of December 31, 2020 and based on current plans, the last to expire issued patent (assuming the issuance of a patent based on our pending patent application) licensed under the PD-L1 and 4-1BB License Agreement is projected to expire in January 2037 and the last to expire issued patent (assuming the issuance of a patent based on our pending patent application) licensed under the OX40 License Agreement is projected to expire in August 2039.

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Chiesi Option Agreement

In May 2019, we entered into the Chiesi Option Agreement with Chiesi Farmaceutici S.p.A., or Chiesi, pursuant to which we granted Chiesi an exclusive option to obtain an exclusive license to develop and commercialize INBRX-101 outside of the United States and Canada. Under the terms of the Chiesi Option Agreement, we received a one-time, non-refundable option initiation payment of $10.0 million in August 2019. If Chiesi exercises its option under the Chiesi Option Agreement, then Chiesi must pay us a one-time, non-refundable fee of $12.5 million upon the effective date of the definitive agreement granting Chiesi the exclusive license.

The option period under the Chiesi Option Agreement began on August 19, 2019. The option period under the Chiesi Option Agreement expires 60 days following the last-to-occur of (a) our delivery to Chiesi of trial phase data for the first Phase I Clinical Trial for INBRX-101 (including the complete clinical study report); (b) our delivery to Chiesi of the finalized minutes from the definitive FDA scientific advice meeting conducted following completion of such Phase I Clinical Trial with the use of the full clinical study report if required by the FDA; and (c) our delivery to Chiesi of the finalized minutes from the definitive parallel EMA-HTA scientific advice meeting conducted following completion of such Phase I Clinical Trial with full use of the clinical study report if required by the EMA. The Chiesi Option Agreement may be terminated by (i) Chiesi upon 30 days’ written notice to us, (ii) either party for the uncured material breach of the other party, and (iii) either party for bankruptcy or other insolvency proceedings of the other party. The Chiesi Option Agreement contains representations, warranties and indemnification provisions customary for similar agreements and arrangements.

Transcenta License Agreement and Technical Services Agreements

On June 21, 2017, we entered into a license agreement, or the Transcenta License Agreement, with Transcenta Holding, Ltd. (formerly Hangzhou Just Biotherapeutics Co., Ltd.), or Transcenta, pursuant to which we granted to Transcenta exclusive, non-transferable rights to develop, manufacture, and sell its products containing our mono-specific protein therapeutic candidate, designed to target DR5, or INBRX-109, or a derivative thereof, within China, Hong Kong, Macau and Taiwan. We also agreed to provide Transcenta with the know-how and materials, including assays and cell lines, necessary to develop the therapeutic candidate. Additionally, pursuant to the Transcenta License Agreement, Transcenta granted to us a royalty-free, worldwide, non-exclusive research license to intellectual property created by Transcenta that incorporates intellectual property we licensed to Transcenta. As payment for the license we granted in the Transcenta License Agreement, we received a non-refundable upfront payment of $2.5 million. In August 2018, the Company achieved the first milestone under the contract for $0.5 million. In June 2019, the Company achieved another milestone under the contract for $1.0 million. Additionally, we are eligible to receive certain developmental and commercial milestone payments of up to an aggregate of approximately $100.0 million, as well as percentage tiered royalties on future product sales with rates ranging between the high single-digits to the low teens.

The Transcenta License Agreement contains representations and warranties, insurance, indemnification and confidentiality provisions customary for similar agreements and arrangements. The term of the Transcenta License Agreement commenced on June 21, 2017, and expires on a country-by-country basis upon the full expiration of Transcenta’s milestone- and royalty-based payment obligations under the Transcenta License Agreement. The royalty payment obligations expire on a product-by-product and country-by-country basis at such time that there is (i) no valid patent claim for the applicable product in the relevant jurisdiction, and (ii) no Generic Product (as defined in this Transcenta License Agreement) of an applicable product available in the relevant jurisdiction. As of December 31, 2020 and based on current plans, the last to expire issued patent (assuming the issuance of a patent based on our pending patent application) licensed under the Transcenta License Agreement is projected to expire in July 2036. The Transcenta License Agreement may be terminated by (i) either party for the uncured material breach of the other party, (ii) either party for bankruptcy or other insolvency proceedings of the other party, and (iii) Transcenta at any time upon 90 days’ written notice to us. In May 2020, we notified Transcenta of potential disputes or disagreements regarding its performance under the Transcenta License Agreement. We are currently in discussions with Transcenta regarding these matters.

On March 19, 2018, we also entered into a technical services agreement, or the March TSA, with Transcenta pursuant to which we provided reasonable assistance with the drug substance transfer between our contract manufacturer and Transcenta. We were reimbursed $0.7 million in April 2018 for the March TSA. The March TSA

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had a six month term and expired in September 2018. On October 6, 2018, we entered into a second technical services agreement, or the October TSA, to provide reasonable assistance pertaining to the transfer of the drug substance between our contract manufacturer and Transcenta. We were reimbursed $0.4 million in October 2018 for the October TSA. The October TSA also had a six month term and expired in April 2019.

Celgene Agreement

As payment for the license granted in the Celgene Agreement, we may be eligible to receive development and regulatory milestones of up to an aggregate of $934.1 million, assuming the achievement of all potential milestones in the Celgene Agreement, as well as percentage tiered royalties based on future worldwide sales, with rates ranging from between the high single-digits to the low teens, subject to potential reduction when and if comparable third-party products attain certain levels of competitive market share (on a country-by-country basis) and, subject to certain limitations, payments to third parties for third-party intellectual property rights. Celgene’s royalty obligations expire (on a country-by-country basis) upon the later of (i) the expiration of the last valid patent claim for the applicable Celgene Licensed Intellectual Property or related product in a country, and (ii) 12 years following that date of the first commercial sale of the applicable Celgene Licensed Intellectual Property or related product in a country. We are obligated to pay 2% of future amounts received under the Celgene Agreement to advisors who assisted us with the negotiations and other matters in connection with the Celgene Agreement.

The Celgene Agreement contains representations and warranties, insurance, indemnification and confidentiality provisions customary for similar agreements and arrangements. In addition, Celgene has the sole right, but not the obligation, to enforce the intellectual property included in the Celgene Agreement.

The term of the Celgene Agreement commenced on July 1, 2013 and expires on a licensed product-by-licensed product and country-by-country basis on the date of expiration of Celgene’s applicable royalty obligations. As of December 31, 2020 and based on our current plans, the last to expire issued patent licensed under the Celgene Agreement is projected to expire in 2033, absent any extension of term. The Celgene Agreement may be terminated by (i) either party for the uncured material breach of the other party, (ii) either party for bankruptcy or other insolvency proceedings of the other party, (iii) Celgene at any time upon 30 days’ written notice to us, and (iv) us, upon Celgene’s, or any of its affiliates’, legal challenge to the validity or enforceability of a licensed patent.

bluebird bio Agreements

The 2018 bluebird Agreement

On December 20, 2018, we entered into a license agreement, or the 2018 bluebird Agreement, with bluebird bio, Inc., or bluebird, pursuant to which we granted to bluebird an exclusive license to use our proprietary sdAb platform to research, develop and commercialize chimeric antigen receptor, or CAR, T-cell therapies. Under the terms of the 2018 bluebird Agreement, we provided bluebird the exclusive worldwide rights to develop, manufacture and commercialize certain cell therapy products containing sdAbs directed to various cancer targets. As payment for the license granted in the 2018 bluebird Agreement, we received a non-refundable upfront payment of $7.0 million. We are also entitled to receive certain developmental milestone payments of up to an aggregate of $51.5 million per therapeutic, as well as percentage tiered royalties on future product sales with rates in the mid-single-digits.

The 2018 bluebird Agreement contains representations and warranties, indemnification and confidentiality provisions customary for similar agreements and arrangements. The term of the 2018 bluebird Agreement commenced on December 20, 2018, and expires on a product-by-product and country-by-country basis upon the full expiration of bluebird’s milestone- and royalty-based payment obligations under the 2018 bluebird Agreement. The royalty obligations under the 2018 bluebird Agreement expire on a product-by-product and country-by-country basis on the later of (i) the expiration of the last valid patent claim for the applicable product in the relevant jurisdiction; (ii) the date on which any applicable regulatory, pediatric, orphan drug or data exclusivity, which provides bluebird with the exclusive right to market the applicable product in the relevant jurisdiction, expires; and (iii) 12 years following that date of the first commercial sale of the applicable product in a country. As of December 31, 2020 and based on current plans, the last to expire issued patent (assuming the issuance of one or more patents based on our pending patent applications) licensed under the 2018 bluebird Agreement is projected to expire in May 2040. The 2018 bluebird Agreement may be terminated by (i) either party for the uncured material breach of the other party,

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(ii) either party for bankruptcy or other insolvency proceedings of the other party, and (iii) bluebird at any time upon 30 days’ written notice to us.

The 2020 bluebird Agreement

On June 9, 2020, we entered into an option and license agreement, or the 2020 bluebird Agreement, with bluebird, pursuant to which we granted to bluebird exclusive worldwide rights to develop binders and cell therapy products containing sdAbs directed to specified targets, consisting of two initial programs and up to an additional 8 programs. Inhibrx retains all rights to the specific sdAbs outside of the cell therapy field. We received a non-refundable upfront option fee of $0.2 million in connection with each of the two initial programs, or $0.4 million in aggregate, and we are entitled to an upfront option fee for each additional program. We also granted to bluebird an option to acquire an exclusive license with respect to all binders and cell therapy products developed under the 2020 bluebird Agreement, which entitles us to additional fees upon exercise of the option.

bluebird may exercise its option on a program-by-program basis during the option term. Additionally, bluebird may extend the option term for up to six months in the event that there are additional bona fide development activities that bluebird desires to undertake. We are also entitled to receive certain developmental milestone payments of up to an aggregate of $51.5 million per therapeutic, as well as percentage tiered royalties on future product sales with rates in the mid-single-digits.

The 2020 bluebird Agreement contains representations and warranties, indemnification and confidentiality provisions customary for similar agreements and arrangements. The term of the 2020 bluebird Agreement commenced on June 9, 2020, and expires on a product-by-product and country-by-country basis upon the full expiration of bluebird’s milestone- and royalty-based payment obligations under the 2020 bluebird Agreement. The royalty obligations under the 2020 bluebird Agreement expire on a product-by-product and country-by-country basis on the later of (i) the expiration of the last valid patent claim for the applicable product in the relevant country; (ii) the date on which any applicable regulatory, pediatric, orphan drug or data exclusivity, which provides bluebird with the exclusive right to market the applicable product in the relevant country, expires; and (iii) 12 years following that date of the first commercial sale of the applicable product in such country. As of December 31, 2020 and based on current plans, the last to expire issued patent (assuming the issuance of one or more patents based on our pending patent applications) licensed under the 2020 bluebird Agreement is projected to expire in May 2040. The 2020 bluebird Agreement may be terminated by (i) either party for the uncured material breach of the other party, (ii) either party for bankruptcy or other insolvency proceedings of the other party, and (iii) bluebird at any time upon prior written notice within a specified number of days before the termination.

WuXi Agreement

On August 28, 2018, we entered into an Amended and Restated Master Services Agreement, as amended by Amendment No. 1 to Amended and Restated Master Services Agreement dated December 11, 2019, or the WuXi Agreement, with WuXi Biologics (Hong Kong) Limited, or WuXi, pursuant to which we agreed, for three years and subject to certain conditions, to exclusively use WuXi to manufacture our therapeutic candidates for which we plan to first initiate clinical studies outside of China. Under the WuXi Agreement, WuXi and certain of its affiliates will provide biologics development and manufacturing services on a project-by-project basis.

Per the terms of the WuXi Agreement, we will own all intellectual property created, developed or reduced to practice by WuXi in the course of providing services to us; provided that, certain intellectual property created or developed by WuXi may be owned exclusively by WuXi if this intellectual property (i) relates to generally applicable experimental methods, (ii) relates to generally applicable manufacturing processes, or (iii) is derivative of WuXi’s pre-existing intellectual property.

Per the terms of the WuXi Agreement, fees will be mutually agreed upon on a project-by-project basis. We also may be eligible to receive discounts in the low- to mid-single digits for certain projects and services per the terms of the WuXi Agreement.

The WuXi Agreement contains representations and warranties, insurance, indemnification and confidentiality provisions customary for similar agreements and arrangements.

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The term of the WuXi Agreement commenced on August 28, 2018 and ends on the date that either party elects to terminate it by providing 30-day written notice to the other party, provided that the WuXi Agreement may only be terminated in this manner if all services requested by pending work orders under the WuXi Agreement have been completed. Work orders commence on the date indicated in each such work order and will terminate upon completion of the services requested therein. Work orders may be terminated by (i) us at any time upon three months’ written notice to WuXi, and (ii) either party for the uncured material breach of the other party, provided that the material breach was not caused by the party terminating the work order.

Intellectual Property

We strive to protect the proprietary technology and information commercially or strategically important to our business. We seek to obtain and maintain, patent rights intended to cover the technologies incorporated into, or used to produce, our therapeutic candidates, the compositions of matter of our therapeutic candidates and their methods of use and manufacture, as well as other inventions that are important to our business. We also seek to obtain strategic or commercially valuable patent rights in the United States and other jurisdictions.

To cover our proprietary technologies and our current pipeline of proprietary products and related methods, such as methods of use, we have filed patent applications representing 39 patent families. As of December 31, 2020, our patent estate, which is solely owned, included 16 issued United States patents, 18 United States pending non-provisional patent applications, 14 United States pending provisional patent applications, 13 pending Patent Cooperation Treaty, or PCT, applications, 164 issued foreign patents and 213 foreign patent applications currently pending in various foreign jurisdictions.

Specifically, we own more than six patent families with claims directed to various sdAb and/or multivalent therapeutic antibodies including, for example, our INBRX-105, INBRX-106, and INBRX-109 therapeutic candidates, and related methods of using the same to treat diseases, e.g., cancer, inflammatory disease, or infectious disease. Patent applications in these families are pending in multiple jurisdictions, including, for example, the United States, Australia, European Patent Organization, Canada, China, Japan, Korea, and Russia; as well as PCT applications and several U.S. provisional applications. Patents in these patent families, if granted, are expected to expire between 2036 and 2039, depending upon their respective filing dates and absent any patent term adjustments or extensions.

We also own two patent families directed to protease inhibitor fusion proteins including, for example, our INBRX-101 therapeutic candidate. Seven United States and 53 foreign patents (Australia, Mexico, Europe (validated in 39 countries), Hong Kong, Japan, South Korea, New Zealand, and Russia) were granted in these families. These patents are expected to expire in 2032 or 2035, absent any patent term extension. Additional patents in this patent family, if granted, are expected to expire in 2032 or 2035, depending upon their respective filing dates and absent any patent term adjustments or extensions.

Additionally, we own two patent families relating to the Celgene Licensed Intellectual Property that are licensed to Celgene. Two United States and 63 foreign patents (Australia, Colombia, China, Europe (validated in 39 countries), Hong Kong, Indonesia, Israel, Japan, South Korea, Mexico, Malaysia, Macao, New Zealand, Peru, Philippines, Russia, Singapore, South Africa and Ukraine) have been granted in these families and include claims directed to anti-CD47 monoclonal antibodies and/or methods of using the same to treat cancer. These patents are expected to expire in 2033, absent any patent term extension. Patent applications in these families are pending in multiple jurisdictions, including, for example, the United States, Australia, European Patent Organization, Canada, China, Japan, South Korea, and Russia. Additional patents in these patent families, if granted, are expected to expire in 2033, depending upon their respective filing dates and absent any patent term adjustments or extensions.

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The following patents (including expected 20 year expiration dates) relate to our fusion protein technologies.

Jurisdiction

Patent Number

Expected Expiration Date

Type

Title

8,986,688

6/28/2032

Composition and method

WAP DOMAIN FUSION POLYPEPTIDES AND METHODS OF USE THEREOF

9,914,765

6/28/2032

Composition

WAP DOMAIN FUSION POLYPEPTIDES AND METHODS OF USE THEREOF

Mexico

356433

6/28/2032

Composition and use

WAP DOMAIN FUSION POLYPEPTIDES AND METHODS OF USE THEREOF

8,980,266

6/28/2032

Composition and method