inbx-20221231


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, 2022

☐ 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 No.)

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 ☒

If securities are registered pursuant to Section 12(b) of the Act, indicate by check mark whether the financial statements of the registrant included in the filing reflect the correction of an error to previously issued financial statements. ☐

Indicate by check mark whether any of those error corrections are restatements that required a recovery analysis of incentive-based compensation received by any of the registrant’s executive officers during the relevant recovery period pursuant to § 240.10D-1(b). ☐

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 June 30, 2022, the aggregate market value of the registrant’s common stock held by non-affiliates of the registrant was approximately $331.2 million, based on the closing price of the registrant’s common stock on the Nasdaq Global Market of $11.35 per share.

As of February 28, 2023, the registrant had 43,572,060 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 2023 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, 2022


	TABLE OF CONTENTS
		Page
Special Note Regarding Forward-Looking Statements		1
Part I.		3
Item 1.	Business	3
Item 1A.	Risk Factors	51
Item 1B.	Unresolved Staff Comments	99
Item 2.	Properties	99
Item 3.	Legal Proceedings	99
Item 4.	Mine Safety Disclosures	99

Part II.		100
Item 5.	Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities	100
Item 6.	Reserved	101
Item 7.	Management’s Discussion and Analysis of Financial Condition and Results of Operations	102
Item 7A.	Quantitative and Qualitative Disclosures About Market Risk	116
Item 8.	Financial Statements and Supplementary Data	117
Item 9.	Changes in and Disagreements With Accountants on Accounting and Financial Disclosure	147
Item 9A.	Controls and Procedures	147
Item 9B.	Other Information	148
Item 9C.	Disclosure Regarding Foreign Jurisdictions that Prevent Inspections	148

Part III		149
Item 10.	Directors, Executive Officers and Corporate Governance	149
Item 11.	Executive Compensation	149
Item 12.	Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters	149
Item 13.	Certain Relationships and Related Transactions, and Director Independence	149
Item 14.	Principal Accountant Fees and Services	149

Part IV.		150
Item 15.	Exhibits and Financial Statement Schedules	150
Item 16.	Form 10-K Summary	154

Signatures		154

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, including whether INBRX-101, or any other product candidate, receives approval from the FDA, or similar regulatory authority, for an accelerated approval process;

•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 and 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 ability to raise funds needed to satisfy our capital requirements, which may depend on financial, economic and market conditions and other factors, over which we may have no or limited control;

•our financial performance;

•our expectations regarding the continued evolution of 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, current market conditions and geopolitical events, such as the ongoing conflict in Ukraine;

•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.

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.

Part I.

Item 1. Business.

Overview

We are a clinical-stage biopharmaceutical company with a pipeline of novel biologic therapeutic candidates, developed using our proprietary modular protein engineering platforms. Our most advanced therapeutic candidate, INBRX-109, is in a potentially registration-enabling study in Chondrosarcoma and we plan to initiate a potentially registration-enabling trial for INBRX-101 in Alpha-1 Antitrypsin Deficiency, or AATD, in the first half of 2023 and a clinical trial in acute Graft-versus -host-disease, or aGvHD, in the second half of 2023.

We leverage our innovative protein engineering technologies and deep understanding of target biology to create therapeutic candidates with attributes and mechanisms superior to current approaches and applicable to a range of challenging, validated targets with high potential.

Our current clinical pipeline includes therapeutic candidates in the following categories:

•INBRX-101 seeks to maintain the natural function of Alpha-1 antitrypsin, or AAT, in a recombinant format, optimized for less frequent dosing and greater potential therapeutic activity as compared to plasma-derived AAT, or pdAAT;

•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; and

•INBRX-105’s mechanism of action is enabled by a multi-specific format that we believe enables programmed death-ligand 1, or PD-L1, targeted 4-1BB agonism.

INBRX-101

INBRX-109

INBRX-106

INBRX-105

AAT-Fc fusion
protein

Tetravalent DR5
agonist

Hexavalent OX40
agonist

PD-L1x4-1BB tetravalent conditional agonist

Program

Therapeutic Area

Target(s)/Format

STAGE OF DEVELOPMENT

Preclinical

Phase 1

Phase 2

Phase 3

INBRX-101*

Orphan/Respiratory

Neutrophil Elastase Inhibitor
AAT-Fusion Protein

INBRX-109**

Oncology

DR5
Tetravalent Agonist

INBRX-106***

Oncology

OX40
Hexavalent Agonist

INBRX-105***

Oncology

PD-L1 x 4-1BB
Tetravalent Conditional Agonist

__________________

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

** 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.

Our Leadership Team

We have assembled a team with deep scientific, manufacturing, and clinical experience in discovering and developing protein therapeutics, as well as an accomplished commercial team with the expertise to successfully bring our therapeutic candidates, if approved, to market. Our in-house capabilities span the disciplines of discovery, protein engineering, cell biology, translational research, chemistry, manufacturing and controls, or CMC, clinical development, and commercialization. Members of our team bring experience from multiple organizations including Genentech, Inc., Gilead Sciences, Inc., Merck & Co., Novartis AG, and Pfizer Inc. 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 biopharmaceutical 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 currently have four clinical therapeutic candidates, each with key data or milestone events expected in 2023. Since entering the clinic, we have made great strides with all of our programs and believe we have the potential to reach the marketplace as soon as 2025 with our first commercial therapeutic.

Apply our protein engineering platforms to create differentiated, next-generation therapeutics in focused disease areas with particular emphasis on oncology.

We continue to focus our internal clinical development where we believe we can create effective and flexible solutions to address the challenges of validated targets in areas with a high unmet medical need. Our modular protein engineering platforms enable us to efficiently identify optional therapeutic formats customized to the target biology.

Maintain our culture of innovation, execution and efficiency.

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.

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, if approved, commercialize successfully and efficiently on our own. Alternatively, we will enter into strategic partnerships in instances where we believe partnering will accelerate our development timelines and/or maximize the worldwide commercial potential of any approved therapeutic candidate.

Our Pipeline

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 and aGvHD.

We believe INBRX-101 for AATD has the potential to be dosed monthly, while maintaining patients in the normal range of AAT exposure, which would be a significant improvement for patients currently receiving weekly plasma-derived AAT infusions that do not maintain normal AAT exposure. Through our proprietary engineering capabilities, we were able to overcome the challenges of producing AAT recombinantly and manufacturing at commercial scale. Additionally, we believe there is an opportunity for INBRX-101 to be used as a treatment for aGvHD. It has the potential for a more sustainable dosing schedule and could provide a superior safety benefit over existing approved therapies coupled with greater efficacy.

Overview of AATD

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.

Unmet Medical Need

This 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 United States Food and Drug Administration, or FDA, allowed for the marketing of direct-to-consumer tests that 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.

We performed a study where functional AAT levels were measured in plasma samples from 65 normal MM genotype individuals. Consistent with other published data, this analysis revealed the 5th and 95th percentiles of functional AAT levels in the normal MM genotype individuals were 21 and 54 µM, respectively, with a median of 36 µM.

Functional AAT levels in 65 healthy volunteers and 30 Phase 1 AAT study participants at baseline prior to dosing of INBRX-101

–Box plots show the minimum, lower quartile, median, upper quartile and maximum.

–The shaded region represents the 5th-95th percentiles of the normal range of functional AAT in healthy MM genotype adults.

–AAT variant determination was conducted by the Mayo Clinic Laboratories using an LC-MS/MS method (A1ALC).

–The Ph 1 baseline data represents the functional AAT levels measured in patients at the beginning of the study prior to dosing of INBRX-101.

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. Even with frequent treatments, the AAT serum concentration following plasma-derived treatment remains considerably below the normal range of 21 to 54 µM as seen in the adaptation graph below that depicts the pharmacokinetic profile of pdAAT based on published data. There is clinical evidence suggesting that maintenance of higher AAT serum trough levels may better protect against lung function decline.

Additionally, there are other significant barriers with the current standard of care for patients with AATD, including under-diagnosis, high cost of chronic augmentation therapy, high patient burden due to frequent infusions, and the inherent risks of receiving human blood products with plasma collection practices that may not be sustainable.

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. 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 scalable yields of active recombinant AAT protein.

Clinical Data

In July 2019, we initiated an open-label, dose escalating Phase 1 trial which was conducted in approximately 10 clinical sites in the United States, the United Kingdom and New Zealand and enrolled a total of 31 patients. The trial was designed as single ascending dose, or SAD, administrations of INBRX-101, with doses of 10 mg/kg, 40 mg/kg, 80 mg/kg or 120 mg/kg, followed by multiple ascending dose, or MAD, administrations of INBRX-101, with doses of 40 mg/kg, 80 mg/kg or 120 mg/kg. These doses were administered every three weeks intravenously to patients diagnosed with AATD who were either treatment naïve or previously treated with pdAAT therapeutics. The primary objective of the trial was safety and tolerability. Secondary objectives included AAT serum exposure, immunogenicity, as measured by frequency of anti-drug antibodies, and NE activity. In addition, we measured pharmacokinetic and pharmacodynamic biomarkers in bronchoalveolar lavage fluid, or BALF, for those patients who received MAD administrations of INBRX-101 at doses of 80 mg/kg or 120 mg/kg.

In March 2022, the FDA granted orphan drug designation for INBRX-101 for the treatment of AATD.

In May 2022, we announced topline results from the Phase 1 trial. Data from this Phase 1 trial included patients with AATD with the ZZ genotype, SZ genotype, and the MZ genotype of the SERPINA1 gene. There were no drug-related severe or serious adverse events. Drug-related adverse events were predominantly mild with a few moderate events and all were transient and reversible. No signs of neutralizing anti-drug antibodies were seen. Dose-related

increases in maximal and total INBRX-101 exposure occurred across the entirety of the single and multiple ascending dose ranges.

The topline data from the multiple ascending dose cohorts of INBRX-101 at 40, 80 and 120 mg/kg IV every three weeks showed the expected accumulation of functional AAT levels. Based on and assuming the accuracy of the PK modeling, accumulation is expected to continue following subsequent doses and to reach a steady-state after a total of approximately five to six consecutive doses, administered every three weeks.

Functional AAT levels over time in AATD patients administered

40, 80 or 120 mg/kg INBRX-101 every three weeks

–Arrows indicate INBRX-101 IV dosing.

–The shaded region represents the normal range of functional AAT in healthy adults.

–Functional AAT samples were not collected immediately following the second dose (Day 21).

–Results shown are from preliminary, unaudited data. Data shown from the 120 mg/kg multiple dose cohort are from the first four evaluable patients; the full dataset is still being collected and analyzed and will be presented at a later date.

The current standard of care, plasma-derived AAT, dosed once weekly at 60 mg/kg, achieves an average concentration, or Cavg, of functional AAT of 17.8 µM over the weekly dosing interval as calculated from steady-state area under the curve, or AUC. INBRX-101 achieved a mean Cavg of functional AAT of 40.4 µM over the 21-day dosing interval following the third 80 mg/kg dose.

In October 2022, we reported BALF data where we observed the post-dose presence of INBRX-101 in every patient and in all three lobes of the lung collected from each of these patients. This data showed emerging evidence of a dose dependent increase of INBRX-101 lung exposure. These BALF samples were from eleven AATD patients in the 80mg/kg and 120mg/kg multiple ascending dose cohorts of the Phase 1 trial and were analyzed using a proprietary and validated mass spectrometry assay developed by Inhibrx to detect INBRX-101 specifically.

Also in October 2022, based on discussions with the FDA, we announced the potential to pursue an accelerated approval pathway in the U.S. for INBRX-101 using functional AAT serum levels as the surrogate endpoint. We plan to initiate a potentially registration-enabling trial during the first half of 2023 with the intent to submit for regulatory approval under the FDA’s Accelerated Approval Program once completed. The FDA also requested additional information to support the correlation between serum AAT levels and the clinical benefit in AATD to further support serum AAT levels as a surrogate endpoint reasonably likely to predict clinical benefit. We are in the process of compiling this data through existing registry, health records and published data and plan to submit those analyses to the FDA as part of the Biologics License Application, or BLA, submission.

Overview of GvHD

Hematopoietic stem cell transplants, or HSCTs, provide an often-curative option for many patients with hematological and oncological conditions, with multiple myeloma, Non-Hodgkin lymphoma, and acute myelogenous leukemia being the most common diseases requiring an HSCT treatment. GvHD is a significant problem that can occur post-surgery, usually after an allogeneic transplant, where the cells donated during the transplant see the recipient’s body as foreign and attack the body. This can lead to substantial morbidity and mortality and remains the most common cause of morbidity and mortality in HSCT. GvHD symptoms range from mild to severe to life threatening and often include skin inflammation, jaundice, and gastrointestinal discomfort, along with other organ problems. Acute cases of GvHD will exist for 100 days or less whereas chronic cases of GvHD can last up to two years.

Unmet Medical Need

Approximately 35-50% of stem cell transplant cases in the United States develop GvHD with a predicted 2028 annual occurrence rate of over 20,000 cases in the United States alone. The current standard of care for GvHD is increased immunosuppression such as methylprednisolone, prednisone and/or other topical steroids. Steroids have a complete response rate of approximately 50%. Those that cannot tolerate steroids explore other emerging options with a relative amount of success, such as kinase inhibitors. However, these options lead to higher complications and the risk of infection is high.

Our Solution: INBRX-101

Strong clinical data and established guidelines for the use of AAT therapy already exist for acute cases of GvHD. Current clinical data for plasma-derived AAT therapies for the treatment of GvHD show promising response rates and favorable safety profiles over approved therapies, but half-life of the therapies is short and therefore requires dosing every two to four days. Based on the observed favorable safety profile of INBRX-101 to date coupled with its extended half-life, we believe INBRX-101 has the potential for greater efficacy due to the ability to dose at higher levels less frequently, while also eliminating the pathogenic risk from plasma-derived products, which can be life threatening in immunocompromised patients susceptible to infection.

We plan to explore this opportunity in a clinical trial to begin during the second half of 2023.

INBRX-109

INBRX-109 is a precisely engineered tetravalent therapeutic candidate targeting death-receptor 5, or DR5, a TNFRSF member, also known as tumor necrosis factor-related apoptosis-inducing ligand, or TRAIL, receptor 2. 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. We have also observed signs of activity with INBRX-109 in combination with standard chemotherapies. Additionally, in June 2021, we initiated a potentially registration-enabling Phase 2 trial for the treatment of unresectable or metastatic conventional chondrosarcoma.

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 the 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 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 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.

Unmet Medical Need

We are currently investigating INBRX-109 in chondrosarcoma, Ewing sarcoma, malignant pleural mesothelioma, colorectal and pancreatic adenocarcinomas. These are some of the most aggressive diseases, some of which are also orphan oncology indications that have shown 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.

Our Solution - INBRX-109

INBRX-109 is a tetravalent agonist of DR5 that we designed with our proprietary single domain antibody, or 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 experience with earlier generation DR5 agonists, 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 and thereby reduce potential hepatotoxicity.

Primary objectives of the Phase 1 trial are safety, tolerability, and determination of the maximum tolerated dose, or 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: Tetravalent DR5 Agonistic Antibody

Clinical Data

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

Ongoing

Dose Range:

0.3 to 30 mg/kg

N= 20

Result:

Maximum tolerated

dose not reached

N=42

Chondrosarcoma

N=20

Mesothelioma with Cisplatin/Carboplatin & Mesothelioma with Cisplatin or Carboplatin and Pemetrexed

N=10

Synovial sarcoma

N=22

Malignant pleural mesothelioma

N=20

Ewing sarcoma with Irinotecan & Temozolomide

N=20

Colorectal cancer

N=20

Pancreatic adenocarcinoma 2nd line with mFOLFIRI

N=10

Gastric adenocarcinoma

N=20

Colorectal cancer with FOLFIRI

N=8

Solid tumors BMI>30

N=20

SDH-deficient solid tumors or GIST with Temozolomide

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

In September 2019, we commenced single agent dose expansion cohorts, Part 2 of this trial. As of February 1, 2023, we have enrolled 117 patients in single agent dose cohorts in the following tumor types: colorectal and gastric adenocarcinomas, malignant pleural mesothelioma, chondrosarcoma, synovial sarcoma, and solid tumors with BMI>30.

Part 3

In February 2021, we initiated chemotherapy combination cohorts in Part 3 of this trial, and have enrolled 64 patients as of February 1, 2023 in malignant pleural mesothelioma, pancreatic adenocarcinoma, Ewing sarcoma, colorectal cancer cohorts, and SDH-deficient solid tumors or GIST cohorts. We expect to announce initial data from these cohorts in 2023.

Initial Results from Phase 1

INBRX-109 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.

In January 2021, the FDA granted Fast Track designation to INBRX-109 for the treatment of patients with unresectable or metastatic conventional chondrosarcoma. In November 2021, the FDA granted orphan drug designation for INBRX-109 for the treatment of conventional chondrosarcoma. In August 2022, the EMA granted orphan drug designation for INBRX-109 for the treatment of conventional chondrosarcoma.

In November 2022, we announced updated efficacy and safety data from the ongoing Phase 1 INBRX-109 expansion cohorts for the treatment of chondrosarcoma. Among the 33 patients evaluable as of November 8, 2022, the observed disease control rate was 87.9%, or 29 out of 33 patients as measured by RECISTv1.1, with two patients achieving partial responses (6.1%) and 27 patients achieving stable disease (81.8%). Disease control was observed in patients with and without IDH1/IDH2 mutations. Of those achieving stable disease, 55.6% had decreases from baseline in tumor size. Clinical benefit was durable, 14 of 33 patients (42.4%) who achieved disease control had a clinical benefit lasting greater than 6 months, and the longest duration of stable disease observed was 20 months. At that time, the median progression-free survival, or PFS, was 7.6 months, and five patients remained on study.

Treatment-related adverse events, or AEs, were reported in less than 5% of the patients with the most common being increased alanine aminotransferase, or ALT, increased aspartate aminotransferase, or AST, and increased blood bilirubin and fatigue. There were no grade 4 or 5 events reported among patients with treatment-related AEs.

Phase 2 INBRX-109 Chondrosarcoma

In June 2021, we initiated a potentially registration-enabling Phase 2 trial in this patient population, which will enroll approximately 200 patients in total at 50 different sites worldwide, with progression free survival, or mPFS, as the primary endpoint. We expect to announce data from this trial during the second half of 2024.

Primary objectives of the ongoing Phase 2 trial are to evaluate the efficacy of INBRX-109 as measured by mPFS, assessed by central real-time independent radiology review. Secondary objectives are to evaluate the overall survival, mPFS by investigator assessment, quality of life, objective response rate, duration of response, disease control rate, safety and tolerability, pharmacokinetics and anti-drug antibodies to INBRX-109.

We are currently in the process of amending the INBRX-109 protocol for the Phase 1 studies and the registration enabling study in conventional chondrosarcoma as a result of the occurrence of a grade 5 hepatotoxicity event. The additional insight gained on patients at risk of significant hepatotoxicity leads us to believe that elderly patients with fatty liver disease are the at-risk population. We plan to implement the Hepatic Steatosis Index, or HSI, into the protocol and exclude elderly patients with an HSI score of 36 or higher.

Recruitment is temporarily paused for new patients while we make this adjustment to the eligibility criteria. This pause in recruitment does not impact around 100 active patients currently on treatment who continue to remain on trial. This partial clinical hold is based on the pre-defined stopping rules, which were built into the trial protocol. We don’t expect this hold to materially affect the trial timelines and anticipate patient enrollment to resume by mid-year.

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

• Unresectable or metastatic

Stratification by line of therapy and IDH1/2 mutation status

⇨

⇨

Until progressive disease (PD) or toxicity

Including

interim analysis

• Primary Endpoint:

progression free survival (PFS)

• Secondary Endpoints:

overall survival (OS), PFS by investigator assessment, quality of life (QoL), objective response rate (ORR), disease control rate (DCR), duration of response (DOR), safety and tolerability, pharmacokinetics, anti-drug antibodies

INBRX-109
N= 134

Placebo

N= 67 (allows for crossover)

Future Clinical Development Plans

We continue to investigate the therapeutic utility of INBRX-109 through a broad clinical development plan across difficult-to-treat cancers. 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.

INBRX-105 AND INBRX-106

INBRX-105 is a conditional tetravelent PD-L1 targeted 4-1BB agonist that is currently being investigated as a single agent and in combination with Keytruda in patients with locally advanced or metastatic solid tumors. INBRX-106 is

a hexavalent OX40 agonist, currently being investigated as a single agent and in combination with Keytruda, a PD-1 blocking checkpoint inhibitor, in patients with locally advanced or metastatic solid tumors.

Background on Immunotherapy

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 marketing approvals in a number of malignancies.

Unmet Medical Need

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 INBRX-105 and INBRX-106 have the potential to combine with the fast-growing immunooncology market, which currently has annual sales of over $20 billion worldwide.

INBRX-105

Background on 4-1BB

4-1BB, or TNFRSF9, a member of the TNFRSF, is a promising co-stimulatory receptor that we believe can synergize with checkpoint inhibitors to address the insufficiency of checkpoint inhibition alone. 4-1BB 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.

Our Solution

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. 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. The image below illustrates the unique structure of INBRX-105:

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

We believe INBRX-105 can overcome the toxicity issues that have limited the success of prior 4-1BB agonists based on its potential to selectively activate 4-1BB + T-cells in the tumor microenvironment, and thus alter the T-cell population, and enrich for cells with anti-tumor capacity. We expect to achieve the maximal therapeutic benefit of INBRX-105 in combination with a PD-1 checkpoint blockade. In our preclinical studies we observed that acute exposure to PD-L1 dependent 4-1BB agonism was sufficient to derive maximal anti-tumor activity when co-dosed with another PD-1 blocking agent at a target saturating dose.

Clinical Data

We initiated a Phase 1/2 clinical trial for INBRX-105 in the United States in February 2019. This 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 22 clinical sites in the United States.

Primary objectives of the Phase 1 trial are safety, tolerability, and the determination of the MTD and recommended Phase 2 dose of INBRX-105 as a single agent and 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 Response Evaluation Criteria in Solid Tumors, or RECIST (version 1.1, or v1.1), 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.

Phase 1/2 INBRX-105 Trial Design and Status

Phase 1/2 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

Complete

Ongoing

Complete

Ongoing

INBRX-105

N=32

INBRX-105

N=62-98

INBRX-105 + Keytruda

N=30

INBRX-105 + Keytruda

N= 105-175

No pre-screening, all-comers

PD-L1+ basket

No pre-screening, all-comers

Multiple cohorts: CPI-naïve and relapsed refractory patients

Part 1, 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.

Part 2, single agent dose expansion, began enrolling during the first quarter of 2021. Part 2 is enrolling between 62 to 98 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 must be positive for PD-L1 expression, as determined by immunohistochemistry, to qualify for enrollment.

Part 3, dose escalation of INBRX-105 in combination with Keytruda, enrolled 30 patients. These patients were not pre-screened for PD-L1 expression.

Part 4 of this trial, INBRX-105 in combination with Keytruda, is enrolling between 105 to 175 patients. Certain patients will be positive for PD-L1 expression and be refractory to or have progressed on prior PD-1 checkpoint inhibitors (NSCLC, melanoma, HNSCC, MSI/TMB-high). Additionally, we will evaluate an additional combination cohort of naive non-small cell lung cancer patients that are positive for PD-L1 expression with a tumor proportion scale of between 1-49%. We expect to announce initial data from the Part 4 combination expansion cohorts in the second half of 2023.

INBRX-106

Background on OX40

OX40, a member of the TNFRSF, 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, the configuration of which we believe to be poorly suited for efficient receptor clustering, evidenced by the lack of clinical responses observed for such molecules.

Our Solution

INBRX-106 is a precisely engineered hexavalent sdAb-based therapeutic candidate targeting OX40, designed to be an optimized agonist of this co-stimulatory receptor. As shown in the diagram below, INBRX-106 is composed of six OX40 targeting sdAbs and a functional Fc domain.

As a hexavalent therapeutic candidate, INBRX-106 is designed to bind six OX40 molecules on the cell surface to mediate efficient receptor clustering and downstream signaling. In preclinical studies, we observed that 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. We also observed that INBRX-106 can mediate T-cell co-stimulation and reduce the suppressive activity of regulatory T-cells. Additionally, INBRX-106 is able to exploit IgG-mediated effector function via the Fc domain.

Clinical Data

We initiated a Phase 1/2 clinical trial in December 2019 for INBRX-106. This trial is designed as an open-label, four-part trial in patients with locally advanced or metastatic solid tumors. We expect the entire trial will be conducted at approximately 19 clinical sites in the United States and enroll over 230 patients. 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 in combination with Keytruda. Secondary objectives are serum exposure, immunogenicity, as measured by the 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.

Phase 1/2 INBRX-106 Trial Design and Status

Phase 1/2 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

Complete

Ongoing

Complete

Ongoing

INBRX-106

N=20

3+3 design

Locally advanced or metastatic solid tumors

All-comers

INBRX-106

N=82-94

0.03 mg/kg (RP2D) Q3W or Q9W, in tumor types responsive to CPIs.

CPI rel/ref

INBRX-106 + Keytruda

N=30

Locally advanced or metastatic solid tumors

mTPI design

>3 subjects per dose level: 0.01, 0.03, 0.1 and 0.3 mg/kg (Q3W)

No prescreening; all-comers

INBRX-106 + Keytruda

N=170

Relapsed or refractory to CPI

PDL1 TPS ≥ 1% (NSCLC)

PDL1 CPS ≥ 1% (PD-L1 basket)

NSCLC PD-L1 TPS>50% or TMB>10/mb

Melanoma

HNSCC

G/GEA

RCC

NSCLC TPS>50% or TMB>10/mb CPI r/r

PDL1+ basket

PDL1+ cutaneous melanoma

PDL1+ uveal melanoma

PDL1+ HNSCC

PDL1+ nasopharyngeal carcinoma

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 in twenty patients. INBRX-106 was observed to be generally well tolerated in humans. The most common adverse effects, or 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.

Part 2 of the trial, single agent dose expansion, administered INBRX-106 in two different dosing schedules to patients with tumor types responsive to checkpoint inhibitors. Utilization of extensive biomarker data guided the determination of what we believe was the optimal dose for Part 2 of the trial, or 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 were 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 1 and 2, we reported observation of stable disease, per investigator assessment, of greater than six months in four out of 10 response evaluable non-small cell lung cancer and melanoma patients. Three of the four patients had

previous exposure to checkpoint inhibitors and one uveal melanoma patient was checkpoint naive. The longest duration of stable disease was 112 weeks in a non-small cell lung cancer patient refractory to Keytruda.

We continue to enroll patients in Part 2 with enrollment expected to be between 82 to 94 patients. We expanded the enrollment for Part 2 in order to increase the dataset in the single agent cohorts. We expect to announce initial data from these cohorts during the first half of 2024.

In Parts 3 and 4 of this trial, INBRX-106 is being evaluated in combination with Keytruda, a PD-1 blocking checkpoint inhibitor. In the all-comer Part 3 of the trial, INBRX-106 was escalated in combination with Keytruda and enrolled 30 patients with locally advance or metastatic solid tumors. It was observed to be well tolerated, with predominantly mild or moderate immune-related toxicities noted. We observed durable responses across multiple tumor types.

In Part 4, INBRX-106 combination expansion cohorts, we are enrolling approximately 170 patients in total who are positive for PD-L1 expression as determined by immunohistochemistry and possessing adequate hematologic and organ function, to qualify for enrollment. Some of these patients will be checkpoint refractory with non-small cell lung cancer (both TPS>1% and >50%), and a basket of other indications as well as uveal melanoma. Additional patients will be checkpoint naive, enrolling patients in each of the following indications: cutaneous melanoma, uveal melanoma, head and neck squamous cell carcinoma, and nasopharyngeal carcinoma. We expect to announce initial data from the dose expansion cohorts in combination with Keytruda during the first half of 2024.

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. 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 candidate 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, 2022, 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.

Chiesi Option Agreement

In May 2019, we entered into an Option Agreement with Chiesi, which was later amended by the First Amendment to Option Agreement, dated August 19, 2019, or the Chiesi Option Agreement, 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. Additionally, the Chiesi Option Agreement provides Chiesi with a right of negotiation for INBRX-101 development and commercialization rights in the United States and Canada in the event we engage in discussions with any third parties for such rights during the term of the Chiesi Option Agreement or, as applicable, the term of a definitive exclusive license agreement between Chiesi and the Company. In August 2019, under the terms of the Chiesi Option Agreement, we received a one-time, non-refundable option initiation payment of $10.0 million. 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. If the option is exercised, under the license agreement, we may be entitled to receive specified milestone payments of up to $122.5 million, as well as royalties on future product sales.

The option period under the Chiesi Option Agreement began on August 19, 2019 and expires 60 days following the last-to-occur of (i) our delivery to Chiesi of trial phase data for the first Phase I Clinical Trial for INBRX-101 (including the complete clinical study report); (ii) 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 (iii) our delivery to Chiesi of the finalized minutes from the definitive parallel European Medicines Agency health technology assessment, or 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, 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, 2022, 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.

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 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

On July 1, 2013, we entered into a license agreement with Celgene, a Bristol Meyers Squibb Company, or Celgene, as amended on November 23, 2018, or the Celgene Agreement, pursuant to which we granted Celgene an exclusive, global license for the development, manufacture and commercialization of our proprietary CD47 binding domain, or the Celgene Licensed Intellectual Property. Per the terms of the Celgene Agreement, Celgene is operationally and financially responsible for the development, manufacturing and commercialization activities of Celgene Licensed Intellectual Property and any additional related antibodies covered by the 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 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, 2022 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.

2seventy Agreements

The 2018 2seventy Agreement

On December 20, 2018, we entered into an exclusive license 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. In November 2021, bluebird assigned the agreement, which we refer to as the 2018 2seventy Agreement, to its affiliate, 2seventy bio, Inc., or 2 seventy, in connection with an internal restructuring and subsequent spin-out of 2seventy. Under the terms of the 2018 2seventy Agreement, we provided 2seventy 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 2seventy Agreement, we received a non-refundable upfront payment of $7.0 million in January 2019. 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. In August 2021, we received a $2.0 million milestone payment under this agreement.

The 2018 2seventy Agreement contains representations and warranties, indemnification and confidentiality provisions customary for similar agreements and arrangements. The term of the 2018 2seventy Agreement commenced on December 20, 2018, and expires on a product-by-product and country-by-country basis upon the full expiration of 2seventy’s milestone- and royalty-based payment obligations under the 2018 2seventy Agreement. The royalty obligations under the 2018 2seventy 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 2seventy 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, 2022 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 2seventy Agreement is projected to expire in May 2040. The 2018 2seventy 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) 2seventy at any time upon 30 days’ written notice to us.

The 2020 2seventy Agreement

On June 9, 2020, we entered into an option and license 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. This agreement, which we refer to as the 2020 2seventy Agreement, was also assigned to 2seventy in November 2021 in connection with bluebird’s internal restructuring and subsequent spin-out of 2seventy. In June 2020, 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. In June 2022, 2seventy selected a third program and paid a non-refundable upfront option fee of $0.2 million in exchange for a development license. Under each of the three programs, we also granted an option in which 2seventy may acquire an exclusive license with respect to all binders and cell therapy products developed under the 2020 2seventy Agreement, which entitles us to additional fees upon exercise of the option. 2seventy may exercise its option on a program-by-program basis during the option term. Additionally, 2seventy may extend the option term for up to six months in the event that there are additional bona fide development activities that 2seventy 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 2seventy Agreement contains representations and warranties, indemnification and confidentiality provisions customary for similar agreements and arrangements. The term of the 2020 2seventy Agreement commenced on June 9, 2020, and expires on a product-by-product and country-by-country basis upon the full

expiration of 2seventy’s milestone- and royalty-based payment obligations under the 2020 2seventy Agreement. The royalty obligations under the 2020 2seventy 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 2seventy 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, 2022, 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 2seventy Agreement is projected to expire in May 2040. The 2020 2seventy 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) 2seventy at any time upon prior written notice within a specified number of days before the termination.

In May 2021, pursuant to the option extension terms in the 2020 2seventy Agreement, bluebird requested to extend the option term for one of the initial programs by an additional six months in exchange for an option extension fee of $0.1 million. In August 2021, pursuant to the option exercise terms in the agreement, bluebird exercised its option to exclusively license one of the initial programs in exchange for an option exercise fee of $2.1 million, the payment of which was received in October 2021.

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 44 patent families. As of December 31, 2022, our patent estate included 22 issued United States patents, 27 United States pending non-provisional patent applications, 14 United States pending provisional patent applications, eight pending Patent Cooperation Treaty, or PCT, applications, 213 issued foreign patents and 358 foreign patent applications currently pending in various foreign jurisdictions.

Specifically, we own more than nine 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 2043, depending upon their respective filing dates and absent any patent term adjustments or extensions.

We also own three patent families directed to protease inhibitor fusion proteins including, for example, our INBRX-101 therapeutic candidate. Eight United States and 63 foreign patents (Australia, Canada, Mexico, Europe (validated in 37 countries), Hong Kong, India, Israel, Japan, South Korea, New Zealand, Russia, and Ukraine) were granted in these families. These patents are expected to expire in 2032 or 2035, absent any patent term extension. Additional patents in these patent families, if granted, are expected to expire in 2032, 2035, or 2043, 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 78 foreign patents (Australia, Chile, Colombia, China, Europe (validated in 39 countries), Eurasia (validated in Russia), Hong Kong, Indonesia, Israel, Japan, South Korea, Mexico, Malaysia, Macao, New Zealand, Peru, Philippines, Singapore, South Africa, Ukraine, and Vietnam) 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, Eurasia, Japan, and South Korea. 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.

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