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Item 1. Business

2024-02-20 compared with 2023-02-21 · 160 added, 223 removed, 256 unchanged (60% of the section changed)

Halozyme Therapeutics, Inc.

is a biopharma technology platform company that provides innovative and disruptive solutions with the goal of improving the patient experience and potentially outcomes.

Our proprietary enzyme, rHuPH20, is used to facilitate the subcutaneous (“SC”) delivery of injected drugs and fluids.

We license our technology to biopharmaceutical companies to collaboratively develop products that combine our ENHANZE ® drug delivery technology (“ENHANZE”) with the partners’ proprietary compounds.

Our first commercially approved product, Hylenex ® recombinant (“Hylenex”), and our ENHANZE partners’ approved products and product candidates are based on rHuPH20, our patented recombinant human hyaluronidase enzyme.

rHuPH20 is the active ingredient in Hylenex , that works by breaking down hyaluronan (“HA”), a naturally occurring carbohydrate that is a major component of the extracellular matrix of the SC space.

is a biopharmaceutical company advancing disruptive solutions to improve patient experiences and outcomes for emerging and established therapies.

As the innovators of ENHANZE ® drug delivery technology (“ENHANZE”) with our proprietary enzyme rHuPH20, our commercially-validated solution is used to facilitate the subcutaneous (“SC”) delivery of injected drugs and fluids, with the goal of reducing the treatment burden for patients.

We license our technology to biopharmaceutical companies to collaboratively develop products that combine ENHANZE with our partners’ proprietary compounds.

We also develop, manufacture and commercialize, for ourselves or with our partners, drug-device combination products using our advanced auto-injector technologies that are designed to provide commercial or functional advantages such as improved convenience, reliability and tolerability, and enhanced patient comfort and adherence.

Our ENHANZE partners’ approved products and product candidates are based on rHuPH20, our patented recombinant human hyaluronidase enzyme.

rHuPH20 works by breaking down hyaluronan (“HA”), a naturally occurring carbohydrate that is a major component of the extracellular matrix of the SC space.

This temporarily reduces the barrier to bulk fluid flow allowing for improved and more rapid SC delivery of high dose, high volume injectable biologics, such as monoclonal antibodies and other large therapeutic molecules, as well as small molecules and fluids.

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and Hoffmann-La Roche, Inc.

(“Roche”), Takeda Pharmaceuticals International AG and Baxalta US Inc (“Takeda”), Pfizer Inc.

(“Roche”), Takeda Pharmaceuticals International AG and Baxalta US Inc.

(“Takeda”), Pfizer Inc.

(“Pfizer”), Janssen Biotech, Inc.

(“Janssen”), AbbVie, Inc.

(“AbbVie”), Eli Lilly and Company (“Lilly”), Bristol-Myers Squibb Company (“BMS”), Alexion Pharma International Operations Unlimited Company (an indirect wholly owned subsidiary of AstraZeneca PLC)(“Alexion”), argenx BVBA (“argenx”), Horizon Therapeutics plc.

(“Horizon”), ViiV Healthcare (the global specialist HIV Company majority owned by GlaxoSmithKline) (“ViiV”) and Chugai Pharmaceutical Co, Ltd (“Chugai”).

(“AbbVie”), Eli Lilly and Company (“Lilly”), Bristol Myers Squibb Company (“BMS”), argenx BVBA (“argenx”), ViiV Healthcare (the global specialist HIV Company majority owned by GlaxoSmithKline) (“ViiV”), Chugai Pharmaceutical Co., Ltd (“Chugai”) and Acumen Pharmaceuticals, Inc.

In addition to receiving upfront licensing fees from our ENHANZE collaborations, we are entitled to receive event and sales-based milestone payments, revenues from the sale of bulk rHuPH20 and royalties from commercial sales of approved partner products co-formulated with ENHANZE.

We currently receive royalties from three of these collaborations, including royalties from sales of one product from the Takeda collaboration, three products from the Roche collaboration and one product from the Janssen collaboration.

Future potential revenues from ENHANZE collaborations and from the sales and/or royalties of our approved products will depend on the ability of our partners, in some areas supported by Halozyme, to develop, manufacture, secure and maintain regulatory approvals for approved products and product candidates and commercialize product candidates.

Through our recent acquisition of Antares Pharma, Inc.

(“Antares”), we also develop, manufacture and commercialize, for ourselves or with our partners, drug-device combination products using our advanced auto-injector technologies.

Also as a result of our acquisition of Antares, our commercial portfolio of proprietary products includes XYOSTED ® , TLANDO ® and NOCDURNA ® .

We currently earn royalties from four of these collaborations, including royalties from sales of one product from the Takeda collaboration, four products from the Roche collaboration, one product from the Janssen collaboration and one product from the argenx collaboration.

We have commercialized auto-injector products with several pharmaceutical companies including Teva Pharmaceutical Industries, Ltd.

(“Teva”), Covis Group S.a.r.l.

(“Covis”) and Otter Pharmaceuticals, LLC (“Otter”).

(“Teva”) and Otter Pharmaceuticals, LLC (“Otter”).

We have development programs including auto-injectors with Idorsia Pharmaceuticals Ltd.

(“Idorsia”) and Pfizer.

Our commercial portfolio of proprietary products includes Hylenex ® , utilizing rHuPH20, and our specialty product XYOSTED ® , utilizing our auto-injector technology.

Our principal offices and research facilities are located at 12390 El Camino Real, San Diego, CA 92130.

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Information found on, or accessible through, our website is not a part of, and is not incorporated into, this Annual Report on Form 10-K.

Our periodic and current reports that we filed with the SEC are available on our website at www.halozyme.com , free of charge, as soon as reasonably practicable after we have electronically filed such material with, or furnished them to, the SEC, including our annual reports on Form 10-K, quarterly reports on Form 10-Q, current reports on Form 8-K and any amendments to those reports.

Our periodic and current reports that we filed with the Securities and Exchange Commission (“SEC”) are available on our website at www.halozyme.com , free of charge, as soon as reasonably practicable after we have electronically filed such material with, or furnished them to, the SEC, including our annual reports on Form 10-K, quarterly reports on Form 10-Q, current reports on Form 8-K and any amendments to those reports.

Our Technology

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HA at the local site reconstitutes its normal density within two days and, therefore, the effect of rHuPH20 on the architecture of the SC space is temporary.

Through our recent acquisition of Antares, our technology also includes pressure-assisted auto-injector technology.

The pressure-assisted auto-injector technology is a form of parenteral drug delivery that continues to gain acceptance and demand among the medical and patient community.

Encompassing a variety of sizes and designs, our technology operates by using pressure to force the drug, in solution or suspension, through the skin and deposits the drug into the SC or intramuscular tissue.

We have designed disposable, pressure-assisted auto-injector devices to address acute and chronic medical needs, such as rheumatoid arthritis and psoriasis, allergic reactions, migraine headaches, testosterone deficiency and maternal health.

Our current platforms include the VIBEX ® and the VIBEX ® QuickShot ® disposable pressure-assisted auto-injection systems, the Vai™ auto-injector and disposable pen injection systems.

Our auto-injectors offer a does capacity ranging from 0.5 mL to 2.25 mL.

Our current platforms include the high-volume auto-injector, VIBEX ® , VIBEX ® QuickShot ® , and Vai™ auto-injectors and multi-does pen injectors, Our current auto-injectors offer a dose capacity ranging from 0.5 mL to 2.25 mL, and our high-volume auto-injector technology extends that dose capacity to at least 10mL.

They are designed for speed and patient comfort and accommodate for highly viscous drug products.

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We are a leader in converting IV biologics to SC delivery and extending the dosing interval of SC drugs, using our commercially-validated ENHANZE technology.

Our ENHANZE technology also has the potential for SC delivery of small molecules, including those developed as long-acting injectables and other therapies that might benefit from larger dose/larger volume SC delivery.

Our ENHANZE technology also has the potential for SC delivery of small molecules and other therapeutic modalities including those developed as long-acting injectables and other therapies that might benefit from larger dose/larger volume SC delivery.

We collaborate with leading pharmaceutical and biotechnology companies to help them develop products that combine our ENHANZE technology with their proprietary compounds.

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In addition, ENHANZE has been demonstrated to enable the combination of two therapeutic antibodies in a single injection, as well as the development of new co-formulation intellectual property.

We leverage our strategic, technical, regulatory and alliance management skills in support of our partners' efforts to develop new subcutaneously delivered products.

We currently have twelve collaborations with five currently approved products and additional product candidates in development using our ENHANZE technology.

We leverage our strategic, technical, regulatory and alliance management skills in support of our partners' efforts to develop new SC delivered products.

We currently have eleven collaborations with seven currently approved products and additional product candidates in development using our ENHANZE technology.

We intend to work with our existing partners to expand our collaborations to add new targets and develop targets and product candidates under the terms of the operative collaboration agreements.

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We leverage our engineering, regulatory and manufacturing skills to support our partners’ plans.

We intend to extend the range of auto-injectors available to current and new partners, initiating development of a high volume auto-injector, and further extend the number of partners by gaining more partners for the current auto-injectors.

We intend to extend the range of auto-injectors available to current and new partners.

In 2023, we completed a successful Phase I clinical study using a high-volume auto-injector.

It is our goal to further extend the number of partners for the current auto-injectors and add new partners for our high-volume auto-injector that utilizes our ENHANZE technology.

Product and Product Candidates

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XYOSTED (testosterone enanthate) Injection

We market and sell in the U.S.

our proprietary product XYOSTED injection for SC administration of testosterone replacement therapy (“TRT”) in adult males for conditions associated with a deficiency or absence of endogenous testosterone (primary or hypogonadism).

XYOSTED is the only FDA-approved SC testosterone enanthate product for once-weekly, at-home self-administration and is approved and marketed in three dosage strengths, 50 mg, 75 mg and 100 mg.

Safety and efficacy of XYOSTED in males less than 18 years old have not been established.

NOCDURNA (desmopressin acetate) Sublingual Tablets

We market and sell NOCDURNA in the U.S., which is the first and only sublingual tablet indicated for the treatment of nocturia due to nocturnal polyuria (“NP”) in adults who awaken at least two times per night to urinate.

In the NOCDURNA clinical trials, NP was defined as night-time urine production exceeding one-third of the 24-hour urine production.

NOCDURNA is a sublingual tablet, marketed in two dosage strengths, that dissolves quickly under the tongue without water and has been shown in clinical studies to reduce nighttime urination by nearly one-half (in patients who average three nighttime bathroom visits.) We license NOCDURNA from Ferring.

In October 2022, we sent a notice to Ferring that we are terminating the NOCDURNA license agreement with an effective termination date in October 2023.

TLANDO (testosterone undecanoate) Oral Formulation

TLANDO is a twice daily oral formulation of testosterone indicated for testosterone replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone (primary or hypogonadotropic hypogonadism).

TLANDO was granted FDA approval in March 2022.

In June 2022, we announced the commercial launch of TLANDO .

Safety and efficacy of TLANDO in males less than 18 years old have not been established.

We market and sell our proprietary product XYOSTED for SC administration of testosterone replacement therapy (“TRT”) in adult males for conditions associated with a deficiency or absence of endogenous testosterone (primary or hypogonadism).

XYOSTED is the only Food and Drug Administration (“FDA”)-approved SC testosterone enanthate product for once-weekly, at-home self-administration and is approved and marketed in the United States (“U.S”).

in three dosage strengths, 50 mg, 75 mg and 100 mg.

We have an ongoing program to develop a proprietary drug device combination product for the endocrinology market, for patients who require additional supplemental hydrocortisone, identified as ATRS-1902.

The development program uses a novel proprietary auto-injector platform to deliver a liquid stable formulation of hydrocortisone.

In June 2021, we submitted an IND application with the FDA for the initiation of a Phase 1 clinical study of ATRS-1902 for adrenal crisis rescue.

The IND application includes the protocol for an initial clinical study to compare the pharmacokinetic profile of our novel formulation of hydrocortisone versus Solu-Cortef ® , which is an anti-inflammatory glucocorticoid and is the current standard of care for the management of acute adrenal crises.

In June 2021, we submitted an investigational new drug (“IND”) application with the FDA for the initiation of a Phase 1 clinical study of ATRS-1902 for adrenal crisis rescue.

The IND application included the protocol for an initial clinical study to compare the pharmacokinetics (“PK”) profile of our novel formulation of hydrocortisone versus Solu-Cortef ® , which is an anti-inflammatory glucocorticoid and is the current standard of care for the management of acute adrenal crises.

In July 2021, the FDA accepted our IND for ATRS-1902 enabling us to initiate our Phase 1 clinical study.

The Phase 1 clinical study, designed to evaluate the safety, tolerability and pharmacokinetics (“PK”) of a liquid stable formulation of hydrocortisone, was initiated in September 2021.

The Phase 1 clinical study, designed to evaluate the safety, tolerability and PK of a liquid stable formulation of hydrocortisone, was initiated in September 2021.

The study was a cross-over design to establish the PK profile of ATRS-1902 (100 mg) compared to Solu-Cortef (100 mg), the reference-listed drug, in 32 healthy adults.

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This formulation utilizes our ENHANZE technology and is administered in two to five minutes, compared to 30 to 90 minutes with the standard IV form.

In September 2018, we announced that Roche received approval from Health Canada for Herceptin SC for the treatment of patients with HER2-positive breast cancer.

In February 2019, we announced that Roche received approval from the U.S.

Food and Drug Administration (“FDA”) for Herceptin SC under the brand name Herceptin Hylecta™ (trastuzumab and hyaluronidase-oysk).

In April 2019, Roche made Herceptin Hylecta available in the U.S.

In October 2022, Roche Pharmaceuticals China announced the approval of Herceptin in China for the treatment of patients with early-stage and metastatic HER2-positive breast cancer.

Herceptin SC has since received approval in Canada, the U.S.

(under the brand name Herceptin Hylecta™) and China.

In June 2020, the FDA approved the fixed-dose combination of Perjeta ® (pertuzumab) and Herceptin for SC injection (Phesgo ® ) utilizing ENHANZE technology for the treatment of patients with HER2-positive breast cancer.

In December 2020, the European Commission (“EC”) also approved Phesgo for the treatment of patients with early and metastatic HER2-positive breast cancer.

In July 2022, Roche submitted the Initial Marketing Application (“IMA”) for the fixed-dose combination of Perjeta (pertuzumab) and Herceptin for SC injection (Phesgo) to Center for Drug Evaluation (“CDE”) in China.

In September 2022, Chugai Pharmaceutical Co., Ltd.

(a Member of the Roche Group) announced the submission of a new NDA in Japan for fixed-dose SC combination of pertuzumab and trastuzumab (same monoclonal antibodies as in Perjeta and Herceptin) with ENHANZE.

This application is based on data from two clinical studies including the results from the global Phase 3 FeDeriCa study in patients with HER2-positive breast cancer.

Phesgo has since received approval in Europe and China.

In September 2023, Chugai Pharmaceuticals Co., Ltd (a Member of the Roche Group) announced that it had obtained regulatory approval for Phesgo from the Ministry of Health, Labour and Welfare (“MHLW”) in Japan.

We will receive royalties for Phesgo sales in Japan as part of our licensing agreement with Roche.

In June 2014, Roche launched MabThera ® SC in Europe for the treatment of patients with common forms of non-Hodgkin lymphoma (“NHL”), followed by launches in additional countries.

This formulation utilizes our ENHANZE technology and is administered in approximately five minutes compared to the approximately 1.5 to 4 hour IV infusion.

This formulation utilizes our ENHANZE technology and is administered in approximately five minutes compared to the approximate 1.5 to 4 hour IV infusion.

In May 2016, Roche announced that the European Medicines Agency (“EMA”) approved MabThera SC to treat patients with chronic lymphocytic leukemia (“CLL”).

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and Canada), for CLL and two types of NHL, follicular lymphoma and diffuse large B-cell lymphoma.

In March 2018, Health Canada approved a combination of rituximab and rHuPH20 (approved and marketed under the brand name RITUXAN ® SC) for patients with CLL.

In November 2022, Roche submitted the IMA for Mabthera SC to CDE in China.

In September 2017, we entered into an agreement with Roche to develop and commercialize one additional exclusive target using ENHANZE technology.

The upfront license payment may be followed by event-based payments subject to Roche’s achievement of specified development, regulatory and sales-based milestones.

In addition, Roche will pay royalties to us if products under the collaboration are commercialized.

In October 2018, we entered into an agreement with Roche for the right to develop and commercialize one additional exclusive target and an option to select two additional targets within four years using ENHANZE technology.

In March 2018, Health Canada approved

a combination of rituximab and ENHANZE (approved and marketed under the brand name RITUXAN ® SC) for patients with CLL.

In November 2022, Roche submitted the independent medical assessment (“IMA”) for MabThera SC to the Center for Drug Evaluation (“CDE”) in China.

In September 2017 and October 2018, we entered into agreements with Roche to develop and commercialize additional exclusive targets using ENHANZE technology.

The upfront license payment may be followed by event-based payments subject to Roche’s achievement of specified development, regulatory and sales-based milestones.

In addition, Roche will pay royalties to us if products under the collaboration are commercialized.

Roche subsequently returned the rights for the first exclusive target.

In December 2018, Roche initiated a Phase 1b/2 study in patients with non-small cell lung cancer for TECENTRIQ ® (atezolizumab) using ENHANZE technology.

In December 2020, Roche initiated a Phase 3 study in patients with non-small cell lung cancer (NSCLC) for TECENTRIQ using ENHANZE technology.

In August 2022, Roche announced that the Phase 3 study met its co-primary endpoints, showing non-inferior levels of Tecentriq in the blood (pharmacokinetics), when injected subcutaneously, compared with IV infusion, in cancer immunotherapy-naïve patients with advanced or metastatic NSCLC for whom prior platinum therapy has failed.

In December 2018, Roche initiated a Phase 1b/2 study in patients with non-small cell lung cancer (“NSCLC”) for TECENTRIQ ® (atezolizumab) using ENHANZE technology, followed by initiation of a Phase 3 study in December 2020.

In August 2022, Roche announced that the Phase 3 study met its co-primary endpoints showing non-inferior levels of Tecentriq in the blood PK, when injected subcutaneously, compared with IV infusion, in cancer immunotherapy-naïve patients with advanced or metastatic NSCLC for whom prior platinum therapy has failed.

The safety profile of the SC formulation was consistent with that of IV Tecentriq.

In November 2022, Roche submitted a Biologics License Application (“BLA”) to the FDA and a Marketing Authorization Application (“MAA”) to the EMA for SC formulation of Tecentriq (atezolizumab) with ENHANZE across all approved indications of IV Tecentriq.

In January 2023, FDA accepted the BLA for the SC formulation of Tecentriq with the official PDUFA goal date of September 15, 2023.

In August 2019, Roche initiated a Phase 1 study evaluating OCREVUS ® (ocrelizumab) with ENHANZE technology in subjects with multiple sclerosis.

In April 2022, Roche initiated a Phase 3 study evaluating OCREVUS with ENHANZE technology in subjects with multiple sclerosis.

In August 2023, Roche announced the approval of Tecentriq SC with ENHANZE by the Medicines and Healthcare products Regulatory Agency (“MHRA”) in Great Britain.

In January 2024, Roche received European Commission (“EC”) marketing authorization for Tecentriq SC for all approved indications of Tecentriq IV.

Roche is expecting Tecentriq SC approval in the U.S.

in September 2024 and is planning to launch soon after.

Tecentriq SC enables SC delivery in approximately seven minutes, compared with 30-60 minutes for IV infusion.

In August 2019, Roche initiated a Phase 1 study evaluating ocrelizumab SC with ENHANZE technology in subjects with multiple sclerosis, followed by initiation of a Phase 3 study in April 2022.

In July 2023, Roche announced that the Phase III OCARINA II trial evaluating ocrelizumab SC with ENHANZE as a twice a year 10-minute SC injection met its primary and secondary endpoints in patients with relapsing forms of multiple sclerosis (“MS”) or primary progressive MS (“RMS” or “PPMS”).

Subsequently, Roche filed ocrelizumab SC with ENHANZE with regulatory authorities in the EU, United Kingdom (“UK”) and the U.S.

In October 2019, Roche nominated a new undisclosed exclusive target to be studied using ENHANZE technology.

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HYQVIA is indicated for the treatment of primary immunodeficiency disorders associated with defects in the immune system.

In May 2013, the EC granted Takeda marketing authorization in all European Union (“EU”) Member States for the use of HYQVIA (solution for SC use) as replacement therapy for adult patients with primary and secondary immunodeficiencies.

In May 2013, the EC granted Takeda marketing authorization in all EU Member States for the use of HYQVIA as replacement therapy for adult patients with primary and secondary immunodeficiencies.

Takeda launched HYQVIA in the first EU country in July 2013 and has continued to launch in additional countries.

In May 2016, Takeda announced that HYQVIA received a marketing authorization from the EC for a pediatric indication.

In September 2014, HYQVIA was approved by the FDA for treatment of adult patients with primary immunodeficiency in the U.S.

HYQVIA is the first SC immune globulin (“IG”) treatment approved for adult primary immunodeficiency patients with a dosing regimen requiring only one infusion up to once per month (every three to four weeks) and one injection site per infusion in most patients, to deliver a full therapeutic dose of IG.

In May 2016, Takeda announced that HYQVIA received a marketing authorization from the EC for a pediatric indication, which was launched in Europe to treat primary and certain secondary immunodeficiencies.

In September 2020, Takeda announced that the EMA approved a label update for HYQVIA broadening its use and making it the first and only facilitated SC immunoglobulin replacement therapy in adults, adolescents and children with an expanded range of secondary immunodeficiencies (“SID”).

In October 2021, Takeda initiated a Phase 1 single-dose, single-center, open-label, three-arm study to assess the tolerability and safety of immune globulin SC (human), 20% solution with ENHANZE (TAK-881) at various infusion rates in healthy adult subjects.

In July 2022, Takeda announced positive topline results from pivotal Phase 3 trial evaluating HYQVIA, for maintenance treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and Takeda confirmed its intention to submit regulatory applications in the United States and European Union in its fiscal year 2022.

In July 2022, Takeda filed a supplemental Biologics License Application (sBLA) for the potential expanded use of HYQVIA for pediatric indication for primary immunodeficiency.

In October 2023, Takeda initiated a Phase 2/3 study to evaluate PK, safety, and tolerability of subcutaneous administration of TAK-881 in adult and pediatric participants with Primary Immunodeficiency Diseases (“PIDD”).

In July 2022, Takeda announced positive topline results from pivotal Phase 3 trial evaluating HYQVIA, for maintenance treatment of chronic inflammatory demyelinating polyneuropathy (“CIDP”).

In June 2023, Takeda announced positive full results from a pivotal Phase 3 trial evaluating HYQVIA for maintenance treatment of CIDP and confirmed regulatory applications were under review in the U.S.

and EU for HYQVIA use as a maintenance therapy in adults with stable CIDP.

In January 2024, Takeda received FDA and EC approval for HYQVIA for the treatment of CIDP as maintenance therapy to prevent the relapse of neuromuscular disability and impairment in adults.

In April 2023, Takeda announced that the FDA-approved the supplemental Biologics License Application (“sBLA”) to expand the use of HYQVIA to treat primary immunodeficiency in children.

In February 2024, Takeda submitted a New Drug Application in Japan seeking approval for TAK-771, subcutaneous 10% human immunoglobulin with ENHANZE, for treatment of primary immunodeficiency.

Pfizer Collaboration

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Targets may be selected on an exclusive basis.

Janssen has elected CD38 as the first target on an exclusive basis.

Janssen has initiated several Phase 3 studies, Phase 2 studies and Phase 1 studies of DARZALEX ® (daratumumab), directed at CD38, using ENHANZE technology in patients with amyloidosis, smoldering myeloma and multiple myeloma.

In February 2019, Janssen’s development partner, Genmab, announced positive Phase 3 trial results from the COLUMBA study evaluating SC DARZALEX in comparison to IV DARZALEX in patients with relapsed or refractory multiple myeloma.

DARZALEX SC ® (utilizing ENHANZE technology) was found to be non-inferior to DARZALEX IV with regard the co-primary endpoints of Overall Response Rate and Maximum Trough concentration.

In May 2020, we announced that Janssen received US FDA approval and launched the commercial sale of DARZALEX FASPRO ® in four regimens across five indications in multiple myeloma patients, including newly diagnosed, transplant-ineligible patients as well as relapsed or refractory patients.

Janssen elected CD38 and initiated several Phase 3 studies, Phase 2 studies and Phase 1 studies of DARZALEX ® (daratumumab), directed at CD38, using ENHANZE technology in patients with amyloidosis, smoldering myeloma and multiple myeloma.

In May 2020, Janssen launched the commercial sale of DARZALEX FASPRO ® (DARZALEX utilizing ENHANZE technology) in four regimens across five indications in multiple myeloma patients, including newly diagnosed, transplant-ineligible patients as well as relapsed or refractory patients.

As a fixed-dose formulation, DARZALEX FASPRO can be administered over three to five minutes, significantly less time than DARZALEX IV which requires multi-hour infusions.

In June 2020, we announced that Janssen received European marketing authorization and launched the commercial sale of DARZALEX SC utilizing ENHANZE in the EU.

Subsequent to these approvals, Janssen received several additional regulatory approvals for additional indications and patient populations in US, EU, Japan and China.

Beginning with the US, in January 2021, Janssen received FDA approval for DARZALEX FASPRO in combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed multiple myeloma patients who are eligible for autologous stem cell transplant.

In January 2021, Janssen received accelerated approval from the FDA for DARZALEX FASPRO in combination with bortezomib, cyclophosphamide and dexamethasone (D-VCd) for the treatment of adult patients with newly diagnosed AL amyloidosis (not recommended for the treatment of patients with AL amyloidosis who have NYHA Class IIIB or Class IV cardiac disease or Mayo Stage IIIB outside of controlled clinical trials).

In July 2021, Janssen received FDA approval for DARZALEX FASPRO in combination with pomalidomide and dexamethasone

(D-Pd) for patients with multiple myeloma after first or subsequent relapse.

In July 2021, Janssen received FDA approval for DARZALEX FASPRO in combination with D-Pd for patients with multiple myeloma after first or subsequent relapse.

In November 2021, Janssen received FDA approval for DARZALEX FASPRO in combination with Kyprolis® (carfilzomib) and dexamethasone for patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy.

In the EU, in June 2021, we announced that Janssen received marketing authorization from the EC for DARZALEX SC in two new indications, in combination with D-VCd in newly diagnosed adult patients with AL amyloidosis and in combination with D-Pd in adult patients with relapsed or refractory multiple myeloma.

In Japan in March 2021, Janssen announced approval from Japan’s Ministry of Health, Labour and Welfare (MHLW) for the SC formulation of DARZALEX (known as DARZQURO) in Japan for the treatment of multiple myeloma, and in May 2021 Janssen commenced commercial sale in Japan.

In August 2021, Janssen received approval of DARZQURO for systemic AL amyloidosis in Japan.

In China in October 2021, Janssen’s DARZALEX FASPRO was approved by the China National Medical Products Administration (NMPA) for the treatment of primary light chain amyloidosis, in combination with D-VCd in newly diagnosed patients.

Subsequent to these approvals, Janssen received several additional regulatory approvals for additional indications and patient populations in the U.S., EU, Japan and China.

Beginning with the U.S., Janssen has marketing authorization for DARZALEX FASPRO in combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed multiple myeloma patients who are eligible for autologous stem cell transplant, in combination with bortezomib, cyclophosphamide and dexamethasone (“D-VCd”) for the treatment of adult patients with newly diagnosed AL amyloidosis, in combination with pomalidomide and dexamethasone (“D-Pd”) for patients with multiple myeloma after first or subsequent relapse, and in combination with Kyprolis ® (carfilzomib) and dexamethasone for patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy.

In the EU, Janssen has marketing authorization for DARZALEX SC in combination with D-VCd in newly diagnosed adult patients with AL amyloidosis and in combination with D-Pd in adult patients with relapsed or refractory multiple myeloma.

In Japan, Janssen has marketing authorization for the SC formulation of DARZALEX (known as DARZQURO in Japan) for the treatment of multiple myeloma and systemic AL amyloidosis.

In China, Janssen has marketing authorization for DARZALEX SC for the treatment of primary light chain amyloidosis, in combination with D-VCd in newly diagnosed patients.

In January 2024, Janssen announced submission of a sBLA to the FDA seeking approval of a new indication for DARZALEX FASPRO in combination with bortezomib, lenalidomide and dexamethasone (“D-VRd”) for induction and consolidation treatment and with lenalidomide (“D-R”) for maintenance treatment of adult patients who are newly diagnosed with multiple myeloma (“NDMM”) and are eligible for autologous stem cell transplant (“ASCT”).

In December 2019, Janssen elected EGFR and cMET as a bispecific antibody (amivantamab) target on an exclusive basis, which is being studied in solid tumors.

In November 2020, Janssen initiated a Phase 1 study of amivantamab and ENHANZE.

In September 2022, Janssen initiated a Phase 3 study of lazertinib and amivantamab with ENHANZE in patients with epidermal growth factor receptor (EGFR)-mutated advanced or metastatic non-small cell lung cancer (PALOMA-3).

In November 2022, Janssen initiated a Phase 2 study of amivantamab with ENHANZE in multiple regimens in patients with advanced or metastatic solid tumors including epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (PALOMA-2).

In September 2022, following a Phase 1 study, Janssen initiated a Phase 3 study of lazertinib and amivantamab with ENHANZE in patients with epidermal growth factor receptor (“EGFR”)-mutated advanced or metastatic non-small cell lung cancer (PALOMA-3).

In November 2022, Janssen initiated a Phase 2 study of amivantamab with ENHANZE in multiple regimens in patients with advanced or metastatic solid tumors including EGFR-mutated non-small cell lung cancer (PALOMA-2).

In January 2024, Janssen noted its intention to submit applications in the U.S.

and EU seeking approval of a SC formulation for amivantamab SC during 2024.

In July 2021, Janssen elected the target HIV reverse transcriptase limited to non-nucleoside reverse transcriptase inhibitors.

In December 2021, Janssen initiated a Phase 1 clinical trial combining rilpivirine and ENHANZE.

Janssen and ViiV are exploring the possibility of an ultra-long acting version of CABENUVA using ENHANZE.

In 2023, Janssen discontinued the rilpivirine program with ENHANZE.

AbbVie Collaboration

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Targets may be selected on an exclusive basis.

AbbVie elected one target on an exclusive basis, TNF alpha, for which it has discontinued development and returned the target.

Lilly Collaboration

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Targets may be selected on an exclusive basis or non-exclusive basis.

BMS has designated multiple immuno-oncology targets including programmed death 1 (PD-1) and has an option to select 3 additional targets by November 2024.

BMS has designated multiple immuno-oncology targets including programmed death 1 (“PD-1”) and has an option to select three additional targets by November 2024.

In October 2019, BMS initiated a Phase 1 study of relatlimab, an anti-LAG-3 antibody, in combination with nivolumab using ENHANZE technology.

In May 2021, BMS initiated a Phase 3 of nivolumab using ENHANZE technology for patients with advanced or metastatic clear cell renal cell carcinoma (CheckMate-67T), leveraging data and insights from Phase 1/2 CA209-8KX study in patients with solid tumors.

In June 2022, BMS nominated a new undisclosed target.

In August 2022, BMS initiated a Phase 3 trial to compare the drug levels of nivolumab with ENHANZE administered subcutaneously vs IV administration in participants with melanoma following complete resection (CheckMate-6GE).

BMS plans to initiate a Phase 3 trial in early 2023 to demonstrate the drug exposure levels of nivolumab and relatlimab fixed-dose combination with ENHANZE is not inferior than intravenous administration in participants with previously untreated metastatic or unresectable melanoma (RELATIVITY-127).

In October 2023, BMS reported positive top-line data from the Phase 3 CheckMate-67T trial evaluating a SC formulation of Opdivo (nivolumab) with ENHANZE in patients with advanced or metastatic clear cell renal cell carcinoma (“ccRCC”) who have received prior systemic therapy.

The study met its co-primary PK endpoints and a key secondary endpoint.

In June 2022, BMS nominated an undisclosed target, which was returned in January 2024.

In March 2023, BMS initiated a Phase 3 trial to demonstrate the drug exposure levels of nivolumab and relatlimab fixed-dose combination with ENHANZE is not inferior to IV administration in participants with previously untreated metastatic or unresectable melanoma (RELATIVITY-127).

Alexion Collaboration

In December 2017, we and Alexion entered into a collaboration and license agreement, under which Alexion has the worldwide license to develop and commercialize products combining our rHuPH20 enzyme with Alexion’s portfolio of products directed at up to four exclusive targets and has access to utilize ENHANZE with up to three exclusive targets.

In December 2017, we and Alexion entered into a collaboration and license agreement (“CLA”), under which Alexion has the worldwide license to develop and commercialize products combining our rHuPH20 enzyme with Alexion’s portfolio of products directed at up to four exclusive targets.

Alexion notified us of a discontinuation of our CLA, effective in the first quarter of 2024.

argenx Collaboration

In February 2019, we and argenx entered into an agreement for the right to develop and commercialize one exclusive target, the human neonatal Fc receptor FcRn, which includes argenx’s lead asset efgartigimod (ARGX-113), and an option to select two additional targets using ENHANZE technology.

In May 2019, argenx nominated a second target to be studied using

ENHANZE technology, a human complement factor C2 associated with the product candidate ARGX-117, which is being developed to treat severe autoimmune diseases in Multifocal Motor Neuropathy (MMN).

In October 2020, we and argenx entered into an agreement to expand the collaboration relationship.

Under the newly announced expansion, argenx gained the ability to exclusively access our ENHANZE technology for three additional targets for a total of up to six targets under the existing and newly expanded collaboration.

In July 2019, argenx dosed the first subject in a phase 1 clinical trial evaluating the safety, pharmacokinetics and pharmacodynamics of efgartigimod (ARGX-113), using ENHANZE technology.

In December 2019, argenx reported that based on data from the phase 1 study and internal company analysis, a one minute injection administered every 2 weeks may be possible.

In December 2020, argenx initiated a Phase 3 study of ARGX-113 using ENHANZE technology for patients with immune thrombocytopenia (ITP), an immune disorder in which the blood does not clot normally.

In January 2021, argenx initiated a Phase 3 study of ARGX-113 using ENHANZE technology in pemphigus vulgaris and foliaceus (PV), a rare autoimmune disease that causes painful blisters on the skin and mucous membranes.

In February 2021, argenx initiated a Phase 3 study of ARGX-113 using ENHANZE technology for patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and initiated a Phase 3 study of ARGX-113 using ENHANZE technology in myasthenia gravis (MG), an autoimmune disorder of the musculoskeletal system caused by IgG autoantibodies.

In December 2021, argenx announced the FDA approval of efgartigimod (VYVGART TM ) for the treatment of generalized myasthenia gravis for the IV dosing regimen.

In March 2022, argenx announced that data from argenx’s phase 3 ADAPT-SC study evaluating SC efgartigimod (1000mg efgartigimod-PH20) for the treatment of generalized myasthenia gravis (gMG) achieved the primary endpoint of total IgG reduction from baseline at day 29, demonstrating statistical non-inferiority to VYVGART (efgartigimod alfa-fcab) IV formulation in gMG patients.

In June 2022, argenx initiated a study, BALLAD, evaluating Efgartigimod with ENHANZE in bullous pemphigoid.

In September 2022, argenx announced the submission of a BLA to the US FDA for SC efgartigimod for the treatment of adults with gMG.

In November 2022, argenx announced the acceptance of the BLA application for SC efgartigimod in gMG with a priority review and a Prescription Drug User Free Act (“PDUFA”) date of March 20, 2023.

In January 2023, argenx announced the review time was extended by the FDA to June 20, 2023 to allow the FDA sufficient time to review.

Argenx has also submitted a marketing authorization application to the European Medicines Agency for SC efgartigimod for the treatment of adults with gMG with an anticipated regulatory approval decision in the fourth quarter of 2023.

In May 2019, argenx nominated a second target to be studied using ENHANZE technology, a human complement factor C2 associated with the product candidate ARGX-117, which is being developed to treat severe autoimmune diseases in Multifocal Motor Neuropathy (“MMN”).

In October 2020, we and argenx entered into an agreement to expand the collaboration relationship, adding three targets for a total of up to six targets under the collaboration.

In December 2021, argenx announced the FDA approval of efgartigimod (VYVGART TM ) for the treatment of generalized myasthenia gravis (“gMG”) for the IV dosing regimen.

In March 2022, argenx announced that data from argenx’s phase 3 ADAPT-SC study evaluating SC efgartigimod utilizing ENHANZE (1000mg efgartigimod-PH20) for the treatment of gMG achieved the primary endpoint of total IgG reduction from baseline at day 29, demonstrating statistical non-inferiority to VYVGART (efgartigimod alfa-fcab) IV formulation in gMG patients.

In June 2023, argenx received FDA approval under the brand name VYVGART ® Hytrulo for the injection with ENHANZE for SC use of treatment of gMG in adult patients who are anti-acetylcholine receptor (“AChR”) antibody positive.

In November 2023, argenx received EC approval of VYVGART SC for the treatment of gMG, which also provides the option for patient self-administration.

In January 2024, argenx received Japan approval for VYVDURA ® (efgartigimod alfa and hyaluronidase-qvfc) co-formulated with ENHANZE for the treatment of adult patients with gMG including options for self-administration.

argenx also expects the regulatory decision on approval of VYVGART SC for gMG in China through Zai Lab by the end of 2024.

In July 2023, argenx reported positive data from the ADHERE study evaluating VYVGART ® Hytrulo with ENHANZE in adults with CIDP.

In February 2024, argenx announced that the FDA had accepted for priority review a sBLA for VYVGART Hytrulo for the treatment of CIDP.

The application has been granted a Prescription Drug User Fee Act (“PDUFA”) action date of June 21, 2024.

argenx also expects to submit VYVGART SC for CIDP for regulatory approval in Japan, Europe, China and Canada in 2024.

In September 2023, Zai Lab limited (argenx commercial partner for China) announced the CDE of the National Medical Products Administration (“NMPA”) granted Breakthrough Therapy Designation for efgartigimod SC for the treatment of patients with CIDP.

In November 2023, argenx reported that the ADVANCE-SC study, evaluating VYVGART ® Hytrulo in adults with primary immune thrombocytopenia (“ITP”) did not meet the primary endpoint of a sustained platelet count response in chronic ITP patients.

In December 2023, argenx reported that the ADDRESS study, evaluating efgartigimod SC in adults with pemphigus vulgaris (“PV”) and pemphigus foliaceus (“PF”) resulted in the proportion of PV patients achieving the primary endpoint of complete remission on a minimal dose of steroids (“CRmin”) was not significantly different between efgartigimod SC and the control arm.

In both studies, patients treated with Efgartigimod PH20 SC achieved the same magnitude of total Immunoglobulin G (“IgG”) reduction as observed in previous clinical trials, reflecting no impact of the route of administration on the study results.

argenx will not pursue additional development in pemphigus.

argenx is currently conducting a Phase 2 study of ARGX-113 (ALKIVIA) using ENHANZE technology for patients with active idiopathic inflammatory myopathy (Myositis) and another study, BALLAD, evaluating ARGX -113 using ENHANZE in bullous pemphigoid.

argenx intends to initiate a registrational trial of ARGX-113 using ENHANZE technology for patients with thyroid eye disease in 2024.

Horizon Collaboration

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In March 2021, Horizon completed dosing in a Phase 1 study exploring the SC formulation of TEPEZZA ® .

The trial was a small, single-dose Phase 1 pharmacokinetic trial which included evaluation of ENHANZE technology for a SC formulation.

The trial was a small, single-dose Phase 1 PK trial which included evaluation of ENHANZE technology for a SC formulation.

In March 2022, Horizon announced the completion of a Phase 1 trial for the TEPEZZA ® SC program.

In October 2023, Horizon became an affiliated entity of Amgen Inc.

Horizon noticed a return of the target and discontinuation of our CLA, effective in the second quarter of 2024.

ViiV Healthcare Collaboration

In June 2021, we entered into a global collaboration and license agreement with ViiV.

The license gives ViiV exclusive access to our ENHANZE technology for four specific small and large molecule targets for the treatment and prevention of HIV.

In June 2021, we and ViiV entered into a global collaboration and license agreement that gives ViiV exclusive access to our ENHANZE technology for four specific small and large molecule targets for the treatment and prevention of HIV.

These targets are integrase inhibitors, reverse transcriptase inhibitors limited to nucleoside reverse transcriptase inhibitors (“NRTI”) and nucleoside reverse transcriptase translocation inhibitors (“NRTTIs”), capsid inhibitors and broadly neutralising monoclonal antibodies (“bNAbs”), that bind to the gp120 CD4 binding site.

In December 2021, ViiV initiated enrollment of a Phase 1 study to evaluate cabotegravir administered subcutaneously with ENHANZE.

In February 2022, ViiV initiated enrollment of a Phase 1 study to evaluate the safety and pharmacokinetics of N6LS, a broadly neutralizing antibody, administered subcutaneously with ENHANZE technology.

In June 2022, ViiV initiated enrollment of a Phase 1 single dose escalation study to evaluate pharmacokinetics, safety and tolerability of long-acting cabotegravir administered subcutaneously with ENHANZE technology.

In February 2022, ViiV initiated enrollment of a Phase 1 study to evaluate the safety and PKs of N6LS, a broadly neutralizing antibody, administered subcutaneously with ENHANZE technology.

In June 2022, ViiV initiated enrollment of a Phase 1 single dose escalation study to evaluate PKs, safety and tolerability of long-acting cabotegravir administered subcutaneously with ENHANZE technology.

In August 2023, ViiV initiated a Phase 2b study to evaluate the efficacy, safety, PKs and tolerability of VH3810109 (N6LS) administered subcutaneously with rHuPH20 in combination with cabotegravir.

In the third quarter of 2023, ViiV initiated a Phase 1 study with ENHANZE for an undisclosed program.

Chugai Collaboration

In March 2022, we entered into a global collaboration and license agreement with Chugai Pharmaceutical Co., Ltd.

The license gives Chugai exclusive access to ENHANZE drug delivery technology for an undisclosed target.

In March 2022, we and Chugai entered into a global collaboration and license agreement that gives Chugai exclusive access to ENHANZE technology for an undisclosed target.

Chugai intends to explore the potential use of ENHANZE for a Chugai drug candidate.

In May 2022, Chugai initiated a Phase 1 study to evaluate the pharmacokinetics, pharmacodynamics, and safety of targeted antibody administered subcutaneously with ENHANZE.

In June 2019, we announced a Cooperative Research and Development Agreement (“CRADA”) with the National Institute of Allergy and Infectious Diseases’ Vaccine Research Center (VRC), part of National Institute of Health (NIH),

enabling the VRC’s use of ENHANZE technology to develop SC formulations of VRC07-523LS and N6LS broadly neutralizing antibodies (bnAbs) against HIV for HIV treatment.

In April 2021, we were notified that the first patient was dosed with N6LS and rHuPH20 in VRC 609 Phase 1 dose-escalation study to evaluate safety, tolerability, and pharmacokinetics of N6LS using ENHANZE technology.

In October 2022, the VRC 609 Phase 1 study was completed.

In September 2020, we entered into a collaboration with the Centre for the AIDS Programme of Research in South Africa (CAPRISA), a non-profit company, to evaluate safety, tolerability and pharmacokinetics of a human monoclonal antibody (CAP256V2LS) in HIV-negative and HIV-positive women in South Africa.

In October 2020, we were notified that the first patient was dosed with CAP256V2LS and rHuPH20 in CAPRISA 012B Phase 1 dose-escalation study to evaluate safety, tolerability, and pharmacokinetics of CAP256V2LS alone and in combination with VRC07-523LS using ENHANZE technology.

In January 2021, we were notified the first patient was dosed with CAP256V2LS and rHuPH20 in combination with VRC07-523LS and rHuPH20 in CAPRISA 012B Phase 1 study.

VRC07-523LS broadly neutralizing antibody was supplied by the NIH/VRC under a research collaboration with CAPRISA.

In June 2022, we received final study reports for CAPRISA 012B Phase 1 study and concluded our collaboration with CAPRISA.

In May 2022, Chugai initiated a Phase 1 study to evaluate the PKs, pharmacodynamics, and safety of targeted antibody administered subcutaneously with ENHANZE.

Acumen Collaboration

In November 2023, we and Acumen entered into a global collaboration and non-exclusive license agreement that provides Acumen access to ENHANZE for a single target.

Acumen intends to explore the potential use of ENHANZE for ACU193, Acumen’s clinical stage monoclonal antibody candidate to target Amyloid-β Oligomers for the treatment of early Alzheimer’s disease.

Device and Other Drug Product Collaborations

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In July 2006, we entered into an exclusive license, development and supply agreement with Teva for an epinephrine auto- injector product to be marketed in the U.S.

Pursuant to the agreement, Teva is obligated to purchase all of its delivery device requirements from us.

We received an upfront cash payment and a milestone payment upon FDA product approval.

We also receive a negotiated purchase price for each device sold, as well as royalties on Teva’s commercial sales of the product.

The agreement will continue until the expiration of the last to expire patent that is filed no later than 12 months after FDA approval.

We have multiple patents that have been granted by the United States Patent and Trademark Office (“USPTO”) that cover this product, the latest of which will expire in 2033.

We have and plan to continue to file patent applications covering this product.

We are the exclusive supplier of the device, which we developed, for Teva’s generic Epinephrine Injection USP products, indicated for emergency treatment of severe allergic reactions including those that are life threatening (anaphylaxis) in adults and certain pediatric patients.

Teva’s Epinephrine Injection, utilizing our patented VIBEX ® injection technology, was approved by the FDA as a generic drug product with an AB rating, meaning that it is therapeutically equivalent to the branded products EpiPen ® and EpiPen Jr ® and therefore, subject to state law, substitutable at the pharmacy.

We supply the device and Teva is responsible for the drug, assembly and packaging, distribution and commercialization of the finished product, for which we also receive royalties on Teva’s net sales.

In December 2007, we entered into a license, development and supply agreement with Teva under which we developed and will supply a disposable pen injector for two therapeutic products:

exenatide and teriparatide.

In December 2007, we entered into a license, development and supply agreement with Teva under which we developed and supply a disposable pen injector for teriparatide.

Under the agreement, we received an upfront payment and development milestones, and are entitled to receive royalties on net product sales by Teva in territories where commercialized.

On February 25, 2022, Teva notified us that it was terminating the exenatide program and related agreement due to a lack of commercial viability.

The termination was effective August 23, 2022.

We are the exclusive supplier of the multi-dose pen, which we developed, used in Teva’s generic teriparatide injection product.

In 2020, Teva launched Teriparatide Injection, the generic version of Eli Lilly’s branded product Forsteo ® featuring our multi-dose pen platform, for commercial sale in several countries outside of the U.S.

Under an exclusive development, license and supply agreement with Teva, we are responsible for the manufacturing and supply of the multi-dose pen used in Teva’s generic teriparatide product and Teva is responsible for the sale and distribution of the product.

We are compensated for devices sold to Teva and we are entitled to receive royalties on net product sales by Teva in the territories.

In November 2012, we entered into a license, supply and distribution agreement with Teva for an auto-injector product containing sumatriptan for the treatment of migraines.

Teva is responsible for the manufacture, supply, commercialization and distribution of the drug, and Halozyme is responsible for the manufacture and supply of the device and assembly and packaging of the finished product.

We are compensated at cost for product shipment to Teva and Teva distributes the product in the U.S.

Teva also received an option for distribution rights in other territories.

In addition, net profits are shared equally between Halozyme and Teva.

The term of the agreement continues seven years from commercial launch, which was in June 2016, with automatic one-year renewals unless terminated sooner by either party in accordance with the terms of the agreement.

Covis Agreements

In September 2014, we entered into a development and license agreement with Covis, to develop and supply a SC auto-injector system for use with Makena, a progestin drug (hydroxyprogesterone caproate) indicated to reduce the risk of preterm birth in women pregnant with one baby and who spontaneously delivered one preterm baby in the past.

Under the agreement, we were granted an exclusive, worldwide, royalty-bearing license, with the right to sublicense, to certain intellectual property rights, including know-how, patents and trademarks.

Covis is responsible for the clinical development and preparation,

submission and maintenance of all regulatory applications, and is responsible for the manufacture and supply of the drug to be used in the product, and to market, distribute and sell the product.

In March 2018, we entered into a manufacturing agreement with Covis for the exclusive supply of the device, a variation of our VIBEX QuickShot SC auto-injector developed by us, and fully assembled and packaged final finished product of the Makena SC auto-injector.

We receive a contracted price per unit on each product manufactured and royalties based on net sales of products commencing on product launch in a particular country.

In October 2020, Covis received notice that the FDA proposed to withdraw approval of Makena (hydroxyprogesterone caproate injection).

Covis requested a public hearing in an effort to maintain patient access to Makena as a treatment option to reduce pre-term birth.

In October 2022 the hearing resulted in the FDA Advisory Committee recommending that Makena should not remain on the market.

In November 2023, Teva announced FDA approval of the generic version of Forteo, featuring our multi-dose auto-injector pen platform for the treatment of osteoporosis among certain women and men.

Pfizer Agreement

In August 2018, we entered into a development agreement with Pfizer to jointly develop a combination drug device rescue pen utilizing the QuickShot auto-injector and an undisclosed Pfizer drug.

Pfizer has provided the intellectual property rights for further development of the product to us and has retained an option to assist in the marketing, distribution and sale if we complete development of the product and submit for regulatory approval.

We are continuing to evaluate the next steps for this program.

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A new chemical entity, selatogrel is being developed for the treatment of a suspected acute myocardial infarction (“AMI”) in adult patients with a history of AMI.

Idorsia will pay for the development of the combination product and will be responsible for applying for and obtaining global regulatory approvals for the product.

The parties intend to enter into a separate commercial license and supply agreement pursuant to which Antares will provide fully assembled and labelled product to Idorsia at cost plus mark-up.

Idorsia will then be responsible for global commercialization of the product, pending FDA or foreign approval.

Halozyme will be entitled to receive royalties on net sales of the commercial product.

Ferring Agreement

In October 2020, we entered into an exclusive license and commercial supply agreement with Ferring for the marketed product NOCDURNA (desmopressin acetate) in the U.S.

Under the terms of the license agreement, we paid Ferring an upfront payment of $5.0 million upon execution and paid an additional $2.5 million on October 1, 2021.

Ferring is eligible for tiered royalties and additional commercial milestone payments potentially totaling up to $17.5 million based on our net sales of NOCDURNA in the U.S.

In October 2022, we sent a notice to Ferring that we are terminating the NOCDURNA license agreement with an effective termination date in October 2023.

Lipocine Agreement

In October 2021, we entered into an exclusive license agreement with Lipocine for the product TLANDO (testosterone undecanoate) in the U.S.

In June 2022, we announced the commercial launch of TLANDO.

Under the terms of the license agreement, we paid Lipocine an upfront payment of $11.0 million.

Lipocine is eligible for additional milestone payments up to $10.0 million and tiered royalty and commercial milestones based on net sales of TLANDO in the U.S.

We will be responsible for the manufacturing and commercialization of TLANDO.

In January 2024, Idorsia disclosed that recruitment of their Phase 3 study with selatogrel for acute myocardial infarction had reached more than 5,500 patients.

Otter Agreement

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Patents and other intellectual proprietary rights are essential to our business.

Our success will depend in part on our ability to obtain patent protection for our inventions, to preserve our trade secrets and to operate without infringing the proprietary

rights of third parties.

Our success will depend in part on our ability to obtain patent protection for our inventions, to preserve our trade secrets and to operate without infringing the proprietary rights of third parties.

Our strategy is to actively pursue patent protection in the U.S.

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Halozyme Patent Portfolio

Our Halozyme patent portfolio includes patents in the U.S., Europe and other countries in the world and we also have numerous pending patent applications.

Our Halozyme patent portfolio includes patents we own solely and, in some cases, jointly with several licensees in the U.S., Europe and other countries in the world and we also have numerous pending patent applications.

In general, patents have a term of 20 years from the application filing date or earlier claimed priority date.

Our issued patents will expire between 2023 and 2039.

We continue to file and prosecute patent applications to strengthen and grow our patent portfolio pertaining to our recombinant human hyaluronidase and other drugs and drug delivery devices, which cover primarily compositions of matter, formulations, methods of use and devices.

We have multiple patents and patent applications throughout the world pertaining to our recombinant human hyaluronidase and methods of use and manufacture, including an issued U.S.

patent which expires in 2027 and an issued European patent which expires in 2024, which we believe cover the products and product candidates under our existing collaborations and Hylenex recombinant.

In addition, we have, under prosecution throughout the world, multiple patent applications that relate specifically to individual product candidates under development, the expiration of which can only be definitely determined upon maturation into our issued patents.

We believe our patent filings represent a barrier to entry for potential competitors looking to utilize these hyaluronidases.

patent which expires in 2027, an issued European patent which expires in 2024, and additional patents that are valid into 2029, which we believe cover the products and product candidates under our existing collaborations and Hylenex recombinant.

In addition, we have, under prosecution throughout the world, multiple patent applications that relate specifically to individual product candidates under development, and jointly owned patent applications relating to our collaborations with several licensees (including, but not limited to, patent applications covering co-formulations and methods of treatment or use that if granted will be valid into the 2040s), the expiration of which can only be definitely determined upon maturation into our issued patents.

We believe our patent filings represent a barrier to entry for potential competitors looking to utilize these hyaluronidases, other drugs and drug delivery devices.

Other Proprietary Rights

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Research and Development Activities

Our research and development expenses consist primarily of costs associated with the product development, quality and regulatory work required to maintain the ENHANZE platform, expenses associated with testing of new auto-injectors, activities and support for our partners in their development and manufacturing of product candidates performed on behalf of our partners, compensation and other expenses for research and development personnel, supplies and materials, facility costs and amortization and depreciation.

Our research and development expenses consist primarily of costs associated with the product development, quality and regulatory work required to maintain the ENHANZE platform, expenses associated with testing of new high-volume auto-injectors, activities and support for our partners in their development and manufacturing of product candidates performed on behalf of our partners, compensation and other expenses for research and development personnel, supplies and materials, facility costs and amortization and depreciation.

We charge all research and development expenses to operations as they are incurred.

Prior to our November 2019 restructuring, our research and development activities were primarily focused on the development of PEGPH20.

Manufacturing

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These manufacturers each produce bulk rHuPH20 under current Good Manufacturing Practices (“cGMP”) for clinical and commercial uses.

Catalent currently produces bulk rHuPH20 for use in Hylenex and collaboration product candidates.

Avid currently produces bulk rHuPH20 for use in collaboration products.

Catalent currently produces bulk rHuPH20 for use in Hylenex and collaboration products and product candidates.

Avid currently produces bulk rHuPH20 for use in collaboration products and product candidates.

We rely on their ability to successfully manufacture these batches according to product specifications.

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and/or (iii) manufacture the bulk rHuPH20 required by us and our partners for use in our proprietary and collaboration products and product candidates.

In addition to supply obligations, Avid and Catalent will also provide support for data and information used in the chemistry, manufacturing and controls sections for FDA and other regulatory filings.

In addition to supply obligations, Avid and Catalent also provide support for data and information used in the chemistry, manufacturing and controls (“CMC”) sections for FDA and other regulatory filings.

We have a commercial manufacturing and supply agreement with Patheon Manufacturing Services, LLC (“Patheon”) under which Patheon will provide the final fill and finishing steps in the production process of Hylenex recombinant.

We also use third parties to manufacture our auto-injector technology products and product candidates, including the products and related components we supply to our partners.

For our products and product candidates, we verify that they are manufactured in accordance with FDA’s cGMPs for drug products and FDA’s current Quality System Regulations (“QSRs”) for medical devices and equivalent provisions in the EU and elsewhere, which are required as part of the overall obligations necessary, in the EU for instance, to obtain a CE-mark.

For our products and product candidates, we verify that they are manufactured in accordance with FDA’s cGMPs for drug products and the FDA’s current Quality System Regulations (“QSRs”) for medical devices and equivalent provisions in the EU and elsewhere, which are required as part of the overall obligations necessary, in the EU for instance, to obtain a CE-mark.

We enter into quality agreements with our third-party manufacturers which require compliance with cGMPs, QSRs and foreign equivalents, to the extent applicable.

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Below is a summary of our key production, manufacturing, assembly and packaging arrangements with third-party manufacturers for products commercialized by us and our partners:

• Phillips-Medisize Corporation (“Phillips”), an international outsource provider of design and manufacturing services, produces commercial quantities of components of our QuickShot auto-injector device for XYOSTED, our QuickShot auto-injector device for the Makena product with Covis, and our VIBEX epinephrine auto-injector product with Teva.

• Phillips-Medisize Corporation (“Phillips”), an international outsource provider of design and manufacturing services, produces commercial quantities of components of our QuickShot auto-injector device for XYOSTED and our VIBEX epinephrine auto-injector product with Teva.

• ComDel Innovation, Inc.

(“ComDel”), a domestic provider of integrated solutions for product development, tooling, and manufacturing, produces commercial quantities of components for the VIBEX sumatriptan auto-injector product and for the teriparatide pen product with Teva.

(“ComDel”), a domestic provider of integrated solutions for product development, tooling, and manufacturing, produces commercial quantities of components for the VIBEX teriparatide auto-injector product with Teva and the VIBEX auto-injector device for the OTREXUP product for Otter.

• Jabil Healthcare, an international manufacturing development company, produces commercial quantities of components of our VIBEX auto-injector device for the OTREXUP product for Otter and the VIBEX epinephrine auto-injector product with Teva.

• Fresenius Kabi supplies commercial quantities of pre-filled syringes of testosterone for XYOSTED.

• Sharp Corporation (“Sharp”), an international contract packaging company, assembles and packages XYOSTED, Sumatriptan Injection USP and the Makena auto-injector products, and the OTREXUP auto-injector product for Otter.

• Pfizer supplies the active pharmaceutical ingredient (“API”) for TLANDO.

• NextPharma, an international pharmaceutical manufacturing company, supplies the bulk capsule product for TLANDO.

• PCI Pharma Services (“PCI”), an international contract packaging company, bottles and packages TLANDO.

• Sharp Corporation (“Sharp”), an international contract packaging company, assembles and packages XYOSTED auto-injector products and the OTREXUP auto-injector product for Otter.

In addition, our Minnetonka, Minnesota facility supports our administrative functions, product development and quality operations and provides additional assembling and warehousing capabilities.

Sales, Marketing and Distribution

We have two teams of sales specialists, one that provide hospital and surgery center customers with the information needed to obtain formulary approval for, and support utilization of, Hylenex recombinant and one that supports the promotion of our testosterone products XYOSTED and TLANDO.

Our commercial activities also include marketing and related services and commercial support services such as commercial operations, managed markets and commercial analytics.

We also employ third-party vendors, such as advertising agencies, market research firms and suppliers of marketing and other sales support related services to assist with our commercial activities.

We sell XYOSTED, TLANDO and Hylenex recombinant in the U.S.

to wholesale pharmaceutical distributors, who sell Hylenex to hospitals and XYOSTED and TLANDO to other end-user customers.

We engage Integrated Commercialization Solutions (ICS), a division of AmerisourceBergen Specialty Group, a subsidiary of AmerisourceBergen, to act as our exclusive distributor for commercial shipment and distribution of Hylenex recombinant to our customers in the United States.

We also contract with numerous wholesale distributors, including Cardinal, McKesson Corporation (“McKesson”) and AmerisourceBergen Corporation to distribute our other proprietary products (including XYOSTED and TLANDO) to retail pharmacies as well as the Veterans Administration and other governmental agencies

In addition to shipping and distribution services, these distributors and third-party logistics provider, Cardinal Health 105, Inc., also known as Specialty Pharmaceutical Services (“Cardinal”) provide us with other key services related to logistics, warehousing, returns and inventory management, sales reports, contract administration and chargebacks processing and accounts receivable management.

We also use a division of Cardinal for sample administration.

We sell XYOSTED and Hylenex recombinant in the U.S.

to wholesale pharmaceutical distributors, who sell Hylenex to hospitals and XYOSTED to other end-user customers.

We engage Integrated Commercialization Solutions (“ICS”), a division of AmerisourceBergen Specialty Group, a subsidiary of AmerisourceBergen, to act as our exclusive distributor for commercial shipment and distribution of Hylenex recombinant to our customers in the U.S.

We also contract with numerous wholesale distributors, including Cardinal, McKesson Corporation (“McKesson”) and AmerisourceBergen Corporation to distribute XYOSTED, to retail pharmacies as well as the Veterans Administration and other governmental agencies.

In addition to shipping and distribution services, these distributors and third-party logistics providers, Cardinal Health 105, Inc., also known as Specialty Pharmaceutical Services (“Cardinal”), and Knipper Health, Inc.

(“Knipper”) provide us with other key services related to logistics, warehousing, returns and inventory management, sales reports, contract administration and chargebacks processing and accounts receivable management.

We also use a division of Cardinal and Knipper for sample administration.

In addition, we utilize these third parties to perform various other services for us relating to regulatory monitoring, including call center management, adverse event reporting, safety database management and other product maintenance services.

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Hylenex recombinant is currently the only FDA-approved recombinant human hyaluronidase on the market.

The competitors for Hylenex recombinant include, but are not limited to, Bausch Health Companies, Inc.’s product, Vitrase ® , an ovine (ram) hyaluronidase, and Amphastar Pharmaceuticals, Inc.’s product, Amphadase ® , a bovine (bull) hyaluronidase.

XYOSTED and TLANDO

The competitors for Hylenex recombinant include Amphastar Pharmaceuticals, Inc.’s product, Amphadase ® , a bovine (bull) hyaluronidase.

In the U.S., there are several different formulations for TRT including intramuscular injection, transdermal patches and gels, oral formulations and nasal gels.

Competition in the U.S.

testosterone replacement market includes transdermal solutions such as AbbVie’s Androgel® 1% and 1.62%, Perrigo’s generic Androgel® Topical Gel, 1.62%, Eli Lilly’s Axiron®, Endo’s Testim® and Fortesta® (and the authorized generic) and Allergan plc’s (“Allergan”) Androderm®.

Potential competition in the U.S.

testosterone replacement market includes transdermal solutions such as AbbVie’s Androgel ® 1% and 1.62%, Perrigo’s generic Androgel ® Topical Gel 1.62%, Eli Lilly’s Axiron ® , Endo’s Testim ® and Fortesta ® (and the authorized generic) and Verity Pharma’s TLANDO ® and Natesto ® .

Other forms of TRT include injectables such as Endo’s Aveed®, Pfizer’s Depo®-Testosterone, and several generic oil testosterone products sold by Actavis, Sandoz, Viatris Inc., Teva and others, as well as Testopel ® pellets by Endo and JATENZO ® , an oral formulation, by Tolmar, and Kyzatrex, an oral formulation by Marius Pharmaceuticals.

We have a wide range of competitors depending upon the branded or generic marketplace, the therapeutic product category, and the product type, including dosage strengths and route of administration.

Our competitors include established specialty pharmaceutical companies, major brand name and generic manufacturers of pharmaceuticals such as Teva, Viatris, Eli Lilly and Endo, as well as a wide range of medical device companies that sell a single or limited number of competitive products or participate in only a specific market segment.

Our competitors include established specialty pharmaceutical companies, major brand name and generic manufacturers of pharmaceuticals such as Teva, Viatris, Eli

Lilly and Endo, as well as a wide range of medical device companies that sell a single or limited number of competitive products or participate in only a specific market segment.

Our competitors also include third party contract medical device design and development companies such as Scandinavian Health Ltd., Ypsomed AG, West Pharmaceutical and Owen Mumford Ltd.

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Diversity and Inclusion

We seek to build and maintain a diverse team of employees that is passionate about and committed to having a positive impact on the lives of patients and their families.

We seek to build and maintain a diverse team of employees that are passionate about and committed to having a positive impact on the lives of patients and their families.

We value and celebrate the unique talents, backgrounds and perspectives each employee contributes to achieving our mission and corporate objectives.

In support of this philosophy, we adopted the Biotechnology Innovation Organization’s principles on workforce development, diversity and inclusion.

Our diverse and inclusive culture is key to attract, develop and retain our talent pool within the globally competitive biotechnology industry.

Our diverse and inclusive culture is key to attracting, developing and retaining our talent pool within the globally competitive biotechnology industry.

Our dedication to these principles has resulted in a diverse and inclusive employee base consisting of 43% female and 29% non-white/Caucasian employees as of February 12, 2024.

As an equal opportunity employer, we strive to attract and connect with diverse talent who best match our core values and who will be successful and thrive at Halozyme.

Our recruiting team partners with hiring managers and we select diverse interview panels to help provide insight at every stage of the process to identify the best possible candidate – whether internal or external – to fill open roles in the company.

As an equal opportunity employer, assuring we have and maintain an inclusive work environment is a key focus area for management.

We actively seek to attract and retain employees who embody and embrace inclusivity as a core value.

Our recruiting team collaborates with hiring managers to find the best possible candidates with appropriate knowledge, experience and technical skills.

These candidates are then carefully vetted by a range of internal stakeholders as part of diverse interview panels.

We evaluate our recruitment and retention efforts based on a variety of metrics, including offer acceptance rate, time-to-hire, turnover and diversity of our employees.

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To support our employees, we conduct an individual development plan process to give employees the opportunity and accountability to document their career goals and discuss the actions necessary to achieve those goals.

We have two internal training programs:

our senior leader development program is focused on advancing business acumen and leadership skills and our learning and development curriculum for the entire organization is focused on personal, professional, team and leadership development opportunities and grounded in our established leadership attributes which identify the knowledge, skills, abilities and behaviors that contribute to individual and organizational performance.

We have three internal training programs:

(i) our senior leader development program is focused on advancing business acumen and leadership skills, (ii) our management development program is focused on strengthening people management capabilities, and (iii) our learning and development curriculum for the entire organization is focused on personal, professional, team and leadership development opportunities and grounded in our established leadership attributes which identify the knowledge, skills, abilities and behaviors that contribute to individual and organizational performance.

In addition, everyone attends or participates in compliance, harassment prevention, and safety training and we offer education assistance for college and university courses, training seminars and educational conference attendance opportunities to all employees.

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Employee Engagement

Building trust and a high performing culture is a top priority for Halozyme.

Building trust and a high performing culture is a top priority for us.

We achieve this by providing a platform for employees to give feedback, collaborate on solutions, and discuss how to make changes to help improve our experience at work.

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Based on the insights gained from past surveys, we have focused on strengthening cross-functional teamwork including how teams communicate and how we hold each other accountable.

Examples of specific actions we have taken in response to employee survey feedback include all-employee training on cross-functional teamwork and a learning series to equip employees to give and receive constructive feedback.

Examples of specific actions we have taken in response to employee survey feedback include all-employee trainings on cross-functional teamwork, accountability and building trust and a learning series to equip employees to give and receive constructive feedback.

Our current focus, based on the latest survey, is to continue to enhance manager leadership and coaching capabilities.

We hold frequent all-employee meetings that serve as an open forum to share progress on strategy and corporate goals as well as potential at-risk areas, celebrate achievements, and share best practices and learnings.

Beginning in 2020 and continuing into 2023 we have increased the frequency of our all-employee meetings from monthly to semi-monthly while transitioning from work-from-home to a hybrid workplace to keep employees well-informed, connected and to provide them with a setting to ask questions and discuss solutions.

These meetings also keep employees well-informed, connected and provide them with a setting to ask questions and discuss solutions.

Management tracks and assesses retention and attrition and interviews departing employees in order to identify any addressable trends.

Compensation & Benefits

Our compensation and benefits programs, with oversight from the Compensation Committee of our Board of Directors, are designed to attract, retain and reward employees through competitive salaries, annual bonus eligibility, long-term incentive awards, Employee Stock Purchase Plan, a 401(k) Plan, healthcare and insurance benefits, health savings and flexible spending accounts, paid time off, family leave, and employee assistance programs.

Our compensation and benefits programs, with oversight from the Compensation Committee of our Board of Directors, are designed to attract, retain and reward employees through competitive salaries, annual bonus eligibility, long-term incentive awards, an Employee Stock Purchase Plan, a 401(k) Plan, healthcare and insurance benefits, health savings and flexible spending accounts, paid time off, family leave, and employee assistance programs.

Each year we conduct surveys to benchmark our salaries and benefits and confirm we are satisfied with the competitiveness of our total compensation offering.

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Employee Health and Safety

We are dedicated to promoting the health and safety of our employees because we believe it fosters employee productivity and job performance.

We have developed and implemented annual workplace safety training which is intended to remind our employees of workplace safety procedures that may be useful in the event of emergency situations and to assist our employees in helping to prevent workplace accidents.

We have a Safety Operations Team which meets on a quarterly basis to review workplace safety and adherence to safety policies.

This team reports safety metrics and results of ongoing initiatives to the CEO semi-annually and the Board annually.

Further, our Code of Conduct emphasizes our commitment to preventing unlawful employment discrimination and workplace harassment including mandatory, on-going sexual harassment training and provides a mechanism for reporting any violations of this policy.

Our response to COVID-19:

Because we take the health and safety of our employees, their families and our local communities very seriously, we continued case monitoring, contact tracing and notifications as required, diagnostic testing and enhanced safety protocols to ensure business continuity and risk of transmission is minimized.

We are committed to protecting the health and safety of our employees, visitors, clients, and the public.

Health and safety practices are integrated into our business processes and align with our Corporate Environmental, Social, Governance program (“ESG”) philosophy and requirements.

We maintain robust health and safety management systems and have established procedures that reduce the risk of injury and ensure compliance with applicable laws and regulations.

Continuous improvement is a key component of our health and safety efforts.

We establish objectives and performance targets and periodically review results both with our internal safety committee as well as at the Executive and Board level to ensure our high standards are maintained.

Our leadership team is active and engaged in supporting our health and safety program.

Our employees are empowered and responsible for integrating health and safety into their daily work activities and we have experienced health and safety professionals on staff to guide these efforts.

Corporate Citizenship

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

What changed 10-K

Item 1. Business