February 2021 EPS Pipeline Report

Home , Abrocitinib, Ansuvimab, Bamlanivimab, Dostarlimab, Everolimus, Ranibizumab

Pipeline Report February 2021

© 2021 Envolve. All rights reserved. Page 1 This quarterly at-a-glance publication is developed by our Clinical Pharmacy Drug Information team to increase your understanding of the drug pipeline, Table of Contents ensuring you’re equipped with insights to prepare for shifts in pharmacy benefit management. In this issue, you’ll learn more about key themes and notable drugs referenced in the following points. COVID-19 1 > Veklury is currently the only agent that is FDA-approved for the treatment of COVID-19. Three additional therapeutics and two vaccines have been granted Emergency Use Authorization (EUA), and at least three more vaccines are Recent Specialty Drug Approvals1 4 expected to receive an EUA in the relatively near future. > The previous quarter noted the approval of several breakthrough therapies for rare or ultra-rare conditions, which previously had no available FDA-approved Recent Non-Specialty Drug Approvals 9 treatments — Zokinvy for Hutchinson-Gilford progeria syndrome and progeroid laminopathies, Oxlumo for primary hyperoxaluria type 1, and Imcivree for genetically mediated obesity. Upcoming Specialty Products 10 > Other notable approvals include: Lupkynis — the first oral therapy approved for lupus nephritis; Orladeyo — the first oral therapy approved as prophylaxis of hereditary angioedema attacks;Cabenuva – the first long-acting injectable antiretroviral therapy intended as maintenance treatment of HIV; and Breyanzi — Upcoming Non-Specialty Products 18 the third CAR-T therapy to market for treatment of large B-cell lymphomas, with a favorable adverse effect profile relative to the two previously approved agents Kymriah and Yescarta. > Other potentially impactful FDA approvals are on the horizon, including teplizumab which would be the first Biosimilars 20 disease-modifying therapy for delaying the onset of type 1 diabetes in high-risk patients, arimoclomol as the first approved therapy for Niemann-Pick disease type C, andcasimersen as the first treatment for Duchenne muscular dystrophy that has mutations amenable to exon 45 skipping. Meanwhile, the FDA’s three-month Generic Specialty Agents 22 delay on the approval decision for aducanumab for mild or prodromal Alzheimer’s disease hints at the willingness to continue its review of the drug, providing hope for the therapy to ultimately be approved. Generic Non-Specialty Agents 23 To prepare this report, our team accesses a wide range of clinical resources. This information is then analyzed, resulting in updates across multiple disease states including recent and anticipated drug approvals, key changes in the biosimilar agent landscape, and notes on recent and anticipated generic product launches. Our pipeline report is just one of many ways we’re committed to providing helpful tools and resources to our clients and partners. We Data is current as of 2.22.2021 look forward to sharing more updates with you in the months ahead.

Ross Hoffman, MD

To provide comments, feedback or requests for report enhancements, please email us at [email protected]. Pipeline Report COVID-19 February 2021

FDA-APPROVED AGENTS FDA Drug Name Manufacturer(s) Approval Therapeutic Class Comments Cost (WAC) Date • Indicated for the treatment of adults and pediatric patients $520 for a 100 mg ≥ 12 years old and weighing ≥ 40 kg requiring hospitalization for single dose vial Veklury COVID-19 $3,120 for a 5-day remdesivir Gilead 10/22/20 Treatment - antiviral course intravenous infusion • Veklury should only be administered in a hospital or healthcare setting capable of providing acute care comparable to inpatient $5,720 for a 10-day hospital care course AGENTS GRANTED FDA EMERGENCY USE AUTHORIZATION (EUA) EUA Drug Name Manufacturer(s) Approval Therapeutic Class Comments Cost (WAC) Date Original: • Current EUA is for the use of high titer convalescent plasma for Convalescent U.S. Dept of Health and 8/23/20 Treatment - blood the treatment of hospitalized patients early in the disease course plasma Unknown at this time Human Services Revised: product and to those hospitalized patients who have impaired humoral intravenous infusion 2/4/21 immunity and cannot produce an adequate antibody response • EUA is for the treatment of mild to moderate COVID-19 in adults and pediatric patients with positive results of direct SARS-CoV-2 $1,250 single dose LY-CoV555 viral testing who are ≥ 12 years old and weighing ≥ 40 kg, and Treatment - infusion bamlanivimab Eli Lilly 11/9/20 who are at high risk for progressing to severe COVID-19 and/or monoclonal antibody $309.60 intravenous infusion hospitalization administration cost • Outpatient only - no cost to patients, although healthcare facilities may charge fees related to administration • EUA for use in combination with Gilead’s Veklury (remdesivir) for treating hospitalized patients with COVID-19 infection in patients Olumiant Treatment - acute aged two years or older, with suspected or laboratory confirmed $2,553 for 14-day baricitinib Eli Lilly 11/19/20 respiratory distress COVID-19 requiring supplemental oxygen, invasive mechanical course oral tablet syndrome (ARDS) ventilation, or extracorporeal membrane oxygenation $91.17 per 2 mg tablet • 4 mg once daily for 14 days or until hospital discharge

EUA Drug Name Manufacturer(s) Approval Therapeutic Class Comments Cost (WAC) Date • EUA is for the treatment of mild to moderate COVID-19 in adults and pediatric patients with positive results of direct SARS-CoV-2 REGN-COV2 viral testing who are ≥ 12 years old and weighing ≥ 40 kg, and $1,500 single dose casirivimab + Treatment - infusion Regeneron 11/21/20 who are at high risk for progressing to severe COVID-19 and/or imdevimab monoclonal antibody hospitalization $309.60 intravenous infusion administration cost • Outpatient only - no cost to patients, although healthcare facilities may charge fees related to administration BNT162b2 • mRNA vaccine that expresses SARS-CoV2 spike protein tozinameran Pfizer 12/11/20 Vaccine $19.50 per dose* intradermal injection • No cost to patients mRNA 1273 • mRNA vaccine that expresses SARS-CoV2 spike protein Moderna 12/18/20 Vaccine $32-37 per dose* intradermal injection • No cost to patients • EUA is for the emergency use of bamlanivimab and etesevimab administered together for the treatment of mild to moderate bamlanivimab: $1,250 LY-CoV555 + LY- coronavirus disease 2019 (COVID-19) in adults and pediatric single dose infusion CoV016 Treatment - patients ( ≥ 12 years of age and weighing ≥ 40 kg) with positive etesevimab: pending bamlanivimab + Eli Lilly 2/9/21 monoclonal antibody results of direct SARS-CoV2 viral testing, and who are at high risk launch etesivimab for progressing to severe COVID-19 and/or hospitalization $309.60 intravenous infusion • Outpatient only - no cost to patients, although healthcare administration cost facilities may charge fees related to administration PIPELINE AGENTS Anticipated Date of Drug Name Manufacturer(s) Therapeutic Class Comments Cost (WAC) EUA or FDA Approval • Non-replicating adenovirus 26-vector dsDNA expressing SARS- Ad26.COV2-S Projected $10 per J&J/Janssen 2/26/21 Vaccine CoV-2 spike protein intradermal injection dose* • No cost to patients *Initially, the federal government will supply the vaccine at no cost to providers.

Anticipated Date of Drug Name Manufacturer(s) Therapeutic Class Comments Cost (WAC) EUA or FDA Approval • Non-replicating chimpanzee adenovirus-vector dsDNA expressing AZD 1222 AstraZeneca Q1 2021 Vaccine SARS-CoV-2 spike protein Projected $3 per dose* intradermal injection • No cost to patients NVX-CoV2373 • SARS-CoV-2 spike glycoprotein nanoparticle + adjuvant vaccine Projected $16 per Novavax Q2 2021 Vaccine intradermal injection • No cost to patients dose*

FDA AcariaHealth and Drug Name Manufacturer(s) Indication(s) Approval PANTHERx Access Comments Cost (WAC) Date Status CARDIOVASCULAR • Approved for use as an adjunct to other low- density lipoprotein-cholesterol (LDL-C) lowering Evkeeza Homozygous familial therapies for the treatment of adult and evinacumab-dgnb Regeneron hypercholesterolemia 2/11/21 Pending pediatric patients aged ≥ 12 years $450,000/year intravenous infusion (HoFH) • Administered as monthly intravenous infusions • Repatha, Juxtapid, and Kynamro are also FDA- approved for HoFH ENDOCRINOLOGY • Approved for use in patients ≥ 12 months of age with a body surface area of ≥ 0.39 m2 for either Hutchinson-Gilford progeria syndrome, or for processing-deficient Progeroid laminopathies with either: heterozygous LMNA mutation Hutchinson-Gilford with progerin-like protein accumulation or Zokinvy progeria syndrome homozygous or compound heterozygous $785,000- lonafarnib Merck 11/20/20 Pending ZMPSTE24 mutations $1,300,000/year oral capsule Progeroid laminopathies • Progeria is an ultra-rare and fatal disease that causes premature aging in children • There are currently no other FDA approved therapies • Projected impact: cost increase • Administered as monthly injections AcariaHealth: limited • Current treatment options for advanced disease Oxlumo 15 kg child: access are very limited, and include frequent renal lumasiran Primary hyperoxaluria $440,000/year Alnylam 11/23/20 dialysis or combined organ transplantation of subcutaneous type 1 70 kg adult: PANTHERx: has liver and kidneys injection $1,320,000/year access • Vitamin B6 has been used as an off-label therapy • Projected impact: cost increase

FDA AcariaHealth and Drug Name Manufacturer(s) Indication(s) Approval PANTHERx Access Comments Cost (WAC) Date Status • Approved for use in patient ≥ 6 years of age Pro-opiomelanocortin (POMC) • POMC and LEPR deficiency obesities are ultra- rare disorders AcariaHealth: limited Imcivree Proprotein convertase • There are approximately 100 to 500 patients access setmelanotide Rhythm subtilisin/ kexin type 1 in the U.S. with POMC deficiency obesity and $119,000- 11/25/20 subcutaneous Pharmaceuticals (PCSK1) approximately 500 to 2,000 patients in the U.S. $356,000/year PANTHERx: has injection with LEPR deficiency obesity access Leptin receptor • There are no approved therapies for these two (LEPR) deficiency conditions obesity • Projected impact: cost increase • Once daily oral prophylaxis therapy approved for patients ≥ 12 years of age Orladeyo • All other HAE therapies are IV or SC injections Hereditary berotralstat BioCryst 12/3/20 Limited access $486,000/year angioedema (HAE) • High demand for this more convenient, less oral capsules invasive dosage form is anticipated • Projected impact: cost replacement of existing therapies HEMATOLOGY • Approved to decrease the incidence of chemotherapy-induced myelosuppression Cosela Cyclin dependent G1 Therapeutics in adult patients when administered prior to trilaciclib kinases (CDK4/CDK6) 2/12/21 Pending Pending launch a platinum/etoposide-containing regimen or intravenous infusion Boehringer Ingelheim inhibitor topotecan-containing regimen for extensive- stage small cell lung cancer (ES-SCLC)

FDA AcariaHealth and Drug Name Manufacturer(s) Indication(s) Approval PANTHERx Access Comments Cost (WAC) Date Status IMMUNOLOGY • Is a structural analog of cyclosporine A, developed to potentially offer some advantage over legacy CNIs, such as improved tolerability AcariaHealth: limited and no need for therapeutic drug level Lupkynis access monitoring voclosporin Aurinia Lupus nephritis 1/22/21 • Would compete with Benlysta for patients with $146,000/year oral capsule PANTHERx: has severe or refractory disease access • Prescribing Information includes black box warnings for malignancies and serious infections • Projected impact: incremental cost increase INFECTIOUS DISEASES

Ebanga • Approved for treatment in both adults and Ridgeback Zaire ebolavirus ansuvimab-zykl 12/21/20 Limited access children Pending launch Biotherapeutics LP infection intravenous infusion • Projected impact: minimal cost increase

• Approved for treatment of adults whose viral load is suppressed (HIV-1 RNA < 50 copies/mL) Cabenuva on a stable regimen, with no history of treatment cabotegravir + ViiV Healthcare failure, and with no known or suspected rilpivirine HIV-1 infection 1/21/21 Pending resistance to either cabotegravir or rilpivirine $48,000/year long-acting Janssen • Once monthly injections after a 4-week oral intramuscular lead-in period injection • Projected impact: cost replacement of existing therapies

FDA AcariaHealth and Drug Name Manufacturer(s) Indication(s) Approval PANTHERx Access Comments Cost (WAC) Date Status ONCOLOGY • Approved for use in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), for the treatment of pediatric patients ≥ 1 year of age and adult patients with AcariaHealth: has relapsed or refractory high-risk disease in the 15 kg child: Danyelza access Year 1: $735,000 YmAbs Therapeutics, bone or bone marrow who have demonstrated naxitamab-gqgk Neuroblastoma 11/25/20 Year 2 and Inc. a partial response, minor response, or stable intravenous infusion PANTHERx: limited disease to prior therapy beyond: access $367,000/year • Prescribing Information includes black box warnings for serious infusion-related reactions and neurotoxicity • Projected impact: incremental cost increase • Approved for use in combination with chemotherapy, for the treatment of adults with metastatic HER2-positive breast cancer who have received two or more prior anti- HER2 regimens, at least one of which was for Margenza metastatic disease margetuximab-cmkb MacroGenics Breast cancer 12/16/20 Pending • Same mechanism of action as Herceptin Pending launch intravenous infusion • Prescribing Information includes black box warnings for left ventricular dysfunction and embryo-fetal toxicity • Projected impact: cost replacement of existing therapies • Approved for the treatment of advanced disease Orgovyx • Will compete with injectable GnRH analog relugolix Myovant Prostate cancer 12/18/20 Limited access therapies such as Lupron $28,000/year oral tablet • Projected impact: cost replacement of existing therapies

FDA AcariaHealth and Drug Name Manufacturer(s) Indication(s) Approval PANTHERx Access Comments Cost (WAC) Date Status • Same indication as Tabrecta • Approved for the treatment of metastatic disease with MET exon 14 skipping alterations

Tepmetko • Estimated prevalence: 84% of all lung cancer Merck Non-small cell lung tepotinib 2/3/21 Pending cases are NSCLC $251,000/year cancer (NSCLC) oral tablet EMD Serono MET exon 14 skipping alterations and MET amplifications are present in 3-4% of NSCLC patients and correlate with poor prognosis • Projected impact: cost replacement of existing therapies • Approved for the treatment of adults with relapsed or refractory MZL after ≥ 1 prior anti- CD20-based regimen, and for relapsed or Marginal zone refractory FL after ≥ 3 prior lines of systemic lymphoma (MZL) Ukoniq therapy umbralisib TG Therapeutics 2/5/21 Pending $191,000/year • Similar indication as Imbruvica for MZL and oral tablet Follicular lymphoma Tazverik for FL (FL) • Estimated prevalence: MZL and FL account for approximately 8% and 20% of all non-Hodgkin lymphoma cases, respectively • Approved for the treatment of adults with relapsed or refractory large B-cell lymphoma after ≥ 2 lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, high-grade B-cell Breyanzi lymphoma, primary mediastinal large B-cell $410,300/one- lisocabtagene Large B-cell Bristol Myers Squibb 2/5/21 Pending lymphoma, and follicular lymphoma grade 3B time therapy maraleucel lymphomas • Is the third CAR-T therapy to market for these intravenous infusion indications, after Kymriah and Yescarta • Has demonstrated a favorable adverse effect profile relative to Kymriah and Yescarta, with lower incidences of cytokine release syndrome and neurotoxicity

Drug Name Manufacturer(s) Indication(s) FDA Approval Date Comments Cost (WAC) CARDIOVASCULAR DISEASE • Approved to reduce the risk of cardiovascular death and HF hospitalization following a hospitalization for HF or need for Verquvo Merck outpatient IV diuretics, in adults with symptomatic chronic HF vericiguat Heart failure (HF) 1/19/21 and ejection fraction < 45% Pending launch oral tablet Bayer • Prescribing information includes a black box warning re: embryo-fetal toxicity DERMATOLOGY Klisyri • For the topical treatment of the face or scalp $990/5-day tirbanibulin Athenex, Inc. Actinic keratosis 12/14/20 course of topical ointment • Five-day course of therapy therapy GENITOURINARY AGENTS • For the treatment of urge urinary incontinence, urgency and Gemtesa Overactive bladder urinary frequency in adults vibegron Urovant Sciences 12/23/20 $5,600/year (OAB) • Once daily oral therapy oral tablet • Multiple other agents exist for the treatment of OAB

Anticipated Drug Name Manufacturer(s) Indication(s) Mechanism of Action(s) Comments Approval Date CARDIOVASCULAR • Potentially large impacted population Revascor* • Proposed for use in left ventricular systolic rexlemestrocel-L Mesoblast Chronic heart failure Stem cell therapy dysfunction 2021 intramyocardial injection • Would be reserved for use in patients who had failed multiple other therapies COAGULATION DISORDERS Ryplazim • There are currently no approved therapies for the Congenital plasminogen Endogenous plasminogen plasminogen Liminal BioSciences treatment of C-PLGD, the estimated prevalence of 3/5/21 deficiency (C-PLGD) analog intravenous infusion which is ~1.6 of every 1,000,000 people AMT-061* • Proposed for the treatment of adults with severe Uniqure etranacogene disease (~40% of the total hemophilia B population) Hemophilia B Gene therapy 2021-2022 dezaparvovec CSL Behring • Current standard of care is factor IX replacement intravenous infusion therapy • Proposed for the treatment of adults with severe Spark SPK-8011* disease (~60% of the total hemophilia A population) Hemophilia A Gene therapy 2021-2022 intravenous infusion Roche • Current standard of care is factor VIII replacement therapy or Hemlibra SB-525* Sangamo • Proposed for the treatment of adults with severe giroctocogene BioSciences Inc disease (~60% of the total hemophilia A population) Hemophilia A Gene therapy 2021-2022 fitelparvovec • Current standard of care is factor VIII replacement intravenous infusion Pfizer therapy or Hemlibra * Expected to cost >$500,000 per member.

Anticipated Drug Name Manufacturer(s) Indication(s) Mechanism of Action(s) Comments Approval Date DERMATOLOGY PF-04965842 • Proposed for the treatment of moderate to severe abrocitinib Pfizer Atopic dermatitis Jnaus kinase 1 (JAK1) inhibitor 4/1/21 disease in patients 12 years of age and older oral tablet CAT354 tralokinumab Leo Pharma Atopic dermatitis IL-13 inhibitor • Would compete with Dupixent for this indication 5/9/21 subcutaneous injection ENDOCRINOLOGY • There are no FDA-approved therapies for MoCD type BBP-870 A, an ultra-rare condition due to an inborn error of Molybdenum cofactor cPMP substrate replacement fosdenopterin BridgeBio Pharma metabolism 3/29/21 deficiency (MoCD) type A therapy intravenous infusion • Infants are most affected, with rapid disease progression and a high infant mortality rate • Fabrazyme, dosed once every two weeks, is also FDA- approved for the treatment of Fabry disease PRX-102 Protalix Enzyme replacement • PRX-102 is being studied as once monthly dosing as pegunigalsidase alfa Fabry disease 4/27/21 Biotherapeutics therapy well as once every two weeks intravenous infusion • Estimated prevalence: 1 in 40,000 to 60,000 males (female prevalence is unknown) • Has been designed for enhanced receptor targeting and enzyme uptake through greater affinity for the NeoGAA* Genzyme M6P receptors on muscle cells, with the aim of avalglucosidase alfa Pompe disease Enzyme replacement therapy enhancing glycogen clearance and improving on the 5/18/21 intravenous infusion Sanofi clinical efficacy achieved with Lumizyme • Estimated prevalence: 50,000 people worldwide BRX345 • There are no FDA-approved therapies for NPC, which Niemann-Pick type C Molecular chaperone arimoclomol Orphazyme has an estimated 500 cases diagnosed worldwide, 6/17/21 disease (NPC) activator oral therapy and which affects ~1 in 120,000 newborns * Expected to cost >$500,000 per member.

Anticipated Drug Name Manufacturer(s) Indication(s) Mechanism of Action(s) Comments Approval Date • Proposed for the delay or prevention of T1D in patients PRV-031 at high-risk of developing the disease Type 1 diabetes (T1D) Anti-CD3 monoclonal teplizumab Provention Bio, Inc. • Administered as one two-week course of therapy 7/2/21 prevention antibody intravenous infusion • Has the potential to be the first disease-modifying therapy for T1D • There are no approved pharmacologic treatment options • PFIC is estimated to affect between one in every 50,000 to 100,000 children born worldwide and A4250 Progressive familial Ileal bile acid transporter causes progressive, life-threatening liver disease odevixibat Albireo Pharma intrahepatic cholestasis 7/20/21 (IBAT) inhibitor oral capsules (PFIC) • Moderate to severe pruritus is a common and problematic clinical presentation of PFIC that can severely diminish quality of life • Data on PFIC types 1, 2, and 3 were submitted to support use across a wide range of patients • Once daily injection proposed for use in children BMN 111 whose growth plates are still open (~25% of the vosoritide C-type Natriuretic Peptide achondroplasia population) BioMarin Achondroplasia 8/20/21 subcutaneous (CNP) analog • The worldwide incidence rate of achondroplasia is injection about one in 25,000 live births • There are no FDA-approved agents for achondroplasia HEMATOLOGY • Proposed for use in both dialysis- and non-dialysis- Evrenzo AstraZeneca Hypoxia-inducible factor dependent CKD Anemia of chronic kidney roxadustat prolyl hydroxylase inhibitor • Would compete with erythropoietin stimulating 3/20/21 disease oral therapy Fibrogen (HIF-PHI) agents (ESAs, e.g., Procrit, Aranesp) • Appears to have less cardiovascular risk

Anticipated Drug Name Manufacturer(s) Indication(s) Mechanism of Action(s) Comments Approval Date • In the Phase 3 PEGASUS study, which met its primary endpoint, pegcetacoplan demonstrated superiority to Soliris with a statistically significant improvement APL-2* Paroxysmal nocturnal C3 and C3b complement in hemoglobin levels at 16 weeks, as well as higher pegcetacoplan Apellis 5/14/21 hemoglobinuria (PNH) inhibition normalization rates across key markers of hemolysis intravenous infusion and clinically meaningful improvement in FACIT- fatigue score, with a comparable safety profile • Estimated prevalence: 0.5-1.5 per 1 million people • Current therapies for ANCA-associated vasculitis CCX168 Anti-neutrophil cytoplasmic C5a complement protein typically include broad immunosuppression with avacopan ChemoCentryx antibody (ANCA)-associated 7/7/21 receptor inhibitor daily doses of glucocorticoids such as prednisone or oral therapy vasculitis (AAV) methylprednisone • Demonstrated ability to dramatically decrease or terminate the need for chronic blood transfusions; • LentiGlobin is also being studied for the treatment of LentiGlobin* sickle cell disease - however, two of the clinical trials betibeglogene Transfusion-dependent for this indication were temporarily suspended to bluebird bio Gene therapy 2022 autotemcel beta-thalassemia (TDT) allow for an investigation into whether two recently intravenous infusion reported cases of cancer are related to the gene therapy. Implications for the product for sickle cell disease as well as for TDT could be serious if a link is found between LentiGlobin therapy and the onset of cancer IMMUNOLOGY KD025 • Demonstrated overall response rates of 73% and Chronic graft-vs-host Rho-associated coiled-coil belumosudil Kadmon Holdings 74% with belumosudil 200 mg QD and 200 mg BID, 5/30/21 disease (cGvHD) kinase 2 (ROCK2) inhibitor oral therapy respectively. In a pivotal trial, was well tolerated MUSCULOSKELETAL CONDITIONS • Proposed for the treatment of patients with mutations Amondys 45* amenable to exon 45 skipping Sarepta Duchenne muscular casimersen Antisense oligonucleotide • Estimated prevalence: 1 in every 3,400 live male births 2/25/21 Therapeutics dystrophy (DMD) intravenous infusion • ~8% of DMD patients are amenable to exon 45 skipping * Expected to cost >$500,000 per member. © 2021 Envolve. All rights reserved. Continued Page 13 Pipeline Report Upcoming Specialty Products February 2021

Anticipated Drug Name Manufacturer(s) Indication(s) Mechanism of Action(s) Comments Approval Date GALGT2* • Would compete with SRP-9001 gene therapy for those AAVrh74.MHCK. Sarepta with mutations between exons 18 and 58 DMD Gene therapy 2021 GALGT2 Therapeutics • SRP-9001 is further along in the pipeline process, but intra-arterial injection comparative safety and efficacy are undetermined • Targets exons 18 through 58 (~60-75% of DMD patients have mutations in these exons) SRP-9001* Sarepta microdystrophin DMD Gene therapy • Topline results from a Phase 2 trial showed benefit 2021 Therapeutics intravenous infusion on the biological endpoint of micro-dystrophin protein expression, but a functional benefit relative to placebo was not demonstrated • One-time treatment • Is the first DMD gene therapy candidate to start PF-06939926* dosing in a Phase 3 trial Pfizer DMD Gene therapy 2022 intravenous infusion • Has become the DMD gene therapy front-runner since SRP-9001 failed to demonstrate a functional benefit in a pivotal trial • Development has been marred by safety issues and SGT-001* Solid Biosciences DMD Gene therapy FDA-applied clinical trial holds, with thus far mediocre 2022 intravenous infusion efficacy results NEUROLOGY • Proposed for treatment of relapsing forms of MS • Will compete with other S1P1 modulators such as RG3477 Selective sphingosine-1- Gilenya, Mayzent, Zeposia ponesimod Janssen Multiple sclerosis (MS) phosphate receptor 1 (S1P1) • Estimated prevalence: 1 million people in the United 3/18/21 oral therapy modulator States • Relapsing MS is the most common form of MS, affecting ~85% of patients BIIB 037 Biogen Amyloid-binding monoclonal • Proposed as a treatment for prodromal or mild stages aducanumab Alzheimer's disease 6/7/21 antibody of Alzheimer's disease intravenous infusion Eisai * Expected to cost >$500,000 per member.

Anticipated Drug Name Manufacturer(s) Indication(s) Mechanism of Action(s) Comments Approval Date • Currently, the only therapeutic option for patients with CALD is allogeneic hematopoietic stem cell transplant (HSCT) Lenti-D* Cerebral • Beneficial effect has been reported if performed early elivaldogene bluebird bio adrenoleukodystrophy Gene therapy in the course of cALD progression Q4 2021 tavalentivec (cALD) intravenous infusion • In the U.S., newborn screening for ALD was added to the Recommended Universal Screening Panel in February 2016 and is currently active in 17 states, accounting for > 58% of U.S. newborns ONCOLOGY • Proposed for the treatment of relapsed or refractory indolent non-Hodgkin lymphoma (NHL), including FL and MZL, after two or more prior lines of systemic therapy Yescarta Follicular lymphoma (FL) • FL is the most common form of indolent lymphoma axicabtagene Gilead CAR-T therapy and the second most common type of lymphoma 3/5/21 ciloleucel Marginal zone lymphoma globally intravenous infusion (MZL) • It accounts for approximately 22% of all lymphomas diagnosed worldwide • MZL is the third most common lymphoma, accounting for 8% to 12% of all B-cell NHLs p1101 ropeginterferon alfa- • Long-acting interferon formulation proposed for PharmaEssentia Monopegylated proline 2b Polycythemia vera (PV) the treatment of PV in the absence of symptomatic 3/15/21 Corporation interferon subcutaneous splenomegaly injection bb2121 bluebird bio • Similar proposed indication as, but apparently B-cell maturation antigen idecabtagene less robust efficacy than, JNJ-68284528, which Multiple myeloma (BCMA)-targeted CAR-T cell 3/27/21 vicleucel Bristol-Myers demonstrated a 97% overall response rate in the therapy intravenous infusion Squibb CARTITUDE-1 trial * Expected to cost >$500,000 per member.

Anticipated Drug Name Manufacturer(s) Indication(s) Mechanism of Action(s) Comments Approval Date • Proposed for treatment of relapsed or refractory Tivopath Multi-kinase inhibitor disease tivozanib AVEO Oncology Renal cell carcinoma 3/31/21 oral therapy Triple VEGF inhibitor • Was more effective than Nexavar (sorafenib) in the TIVO-1 trial • Proposed for the treatment of recurrent or advanced TSR-042 Tesaro Anti-PD-1 monoclonal disease that has progressed on or after a platinum- dostarlimab Endometrial cancer 4/14/21 antibody based regimen, including microsatellite instability intravenous infusion GlaxoSmithKline high tumors Lonca Antibody-drug conjugate • Similar CD19-targeted mechanism of action as Diffuse large B-cell loncastuximab tesirine ADC Therapeutics containing anti-CD19 Monjuvi (tafasitamab-cxix), which is also FDA- 5/21/21 lymphoma (DLBCL) intravenous infusion monoclonal antibody approved for use in relapsed/refractory DLBCL • Proposed for use as second-line treatment of advanced or metastatic disease with FGFR2 genetic aberrations BBP831 Pan-fibroblast growth factor • FGFR2 genetic aberrations are present in infigratinib BridgeBio Pharma Cholangiocarcinoma receptor (FGF-R) kinase 6/1/21 approximately 15% to 20% of people who have this oral capsule inhibitor disease • Currently Pemazyre is the only other FDA-approved agent • Proposed for the treatment of patients with high-risk Hematopoietic stem disease, specifically those patients who have persistent OMS721 cell transplant- TMA despite modification of immunosuppressive Omeros Anti-MASP-2 monoclonal narsoplimab associated thrombotic therapy 7/17/21 Corporation antibody intravenous infusion microangiopathy (HSCT- • Approximately 20,000 HSCT procedures are performed TMA) in the U.S. annually, and TMA is reported to occur in approximately 10% to 25% of HSCT patients • Proposed for the treatment of adults with locally advanced or metastatic disease who have progressed MGA012 Squamous cell carcinoma on, or who are intolerant of, platinum-based retifanlimab Incyte PD-1 inhibitor 7/25/21 of the anal canal (SCAC) chemotherapy intravenous infusion • Although SCAC is a rare disease, its incidence is thought to be increasing * Expected to cost >$500,000 per member.

Anticipated Drug Name Manufacturer(s) Indication(s) Mechanism of Action(s) Comments Approval Date Rolontis • Long-acting agent dosed every 3 weeks eflapegrastim Spectrum Chemotherapy-induced Granulocyte colony • Demonstrated non-inferiority to Neulasta 1st Half of 2021

subcutaneous Pharmaceuticals neutropenia stimulating factor • Is currently being studied with dosing on the same injection day as chemotherapy • Proposed for the treatment of relapsed/refractory JNJ-68284528 disease after at least three prior lines of therapy ciltacabtagene Janssen Multiple myeloma Anti-BCMA CAR-T therapy • Demonstrated a 97% overall response rate and 67% 1st Half of 2021 autoleucel achieved a stringent complete response (sCR) at intravenous infusion a median follow-up of 12.4 months in the Phase I/II CARTITUDE-1 trial Controlled IL-12* • Current standard of care is surgery, followed Ad-RTS-hIL-12/ by radiation and chemotherapy (usually with Gene therapy + oral activator veledimex Ziopharm Oncology Recurrent glioblastoma temozolomide) 2021-2022 agent intratumoral injection • Would potentially be used after resection and + oral therapy radiation + temozolomide if progression or recurrence OPHTHALMOLOGY • Confirmation of diagnosis will be key, as clinical NSR-REP1* Nightstar Choroideremia Gene therapy presentation of this disease is similar to other 2021 subretinal injection conditions * Expected to cost >$500,000 per member.

Anticipated Drug Name Manufacturer(s) Indication(s) Mechanism of Action(s) Comments Approval Date DERMATOLOGY NexoBrid Teva • Proposed for debridement in adults bromelain Burn wound debridement Enzyme with deep partial-thickness and/or 6/29/21 topical gel MediWound full-thickness thermal burns INFECTIOUS DISEASE • Is being developed as a potential brincidofovir medical countermeasure for Chimerix Smallpox Viral DNA polymerase inhibitor 4/7/21 oral therapy smallpox in the event of a bioterror attack SCY-078 ibrexafungerp Glucan synthase inhibitor - • Proposed for both treatment and Scynexis Vulvovaginal candidiasis (VVC) 6/1/21 intravenous infusion & triterpenoid prevention of recurrent VVC oral therapy MUSCULOSKELETAL • Subcutaneous administration by RN624 a health care provider once every tanezumab eight weeks Pfizer Osteoarthritis Nerve growth factor (NGF) inhibitor Q2 2021 subcutaneous • Intended for use in patients who injection have experienced inadequate pain control with other analgesics NEPHROLOGY RDX5791 • Proposed for the control of serum Chronic kidney disease (CKD)-related Sodium hydrogen exchanger 3 tenapanor Ardelyx phosphorus in adult patients with 4/29/21 hyperphosphatemia (NHE3) inhibitor oral therapy CKD on dialysis • Proposed to reduce the risk of BAY 94-8862 chronic kidney disease progression, finerenone Bayer Chronic kidney disease (CKD) Nerve growth factor (NGF) inhibitor 7/12/21 kidney failure or kidney death in oral therapy patients with Type 2 diabetes

Anticipated Drug Name Manufacturer(s) Indication(s) Mechanism of Action(s) Comments Approval Date PSYCHIATRY LY03005 Attention deficit hyperactivity Serotonin norepinephrine • Multiple other therapies for ADHD ansofaxine Luye Pharma Group Q1 2021 disorder (ADHD) modulating agent (SNMA) are currently available oral tablets ALKS 3831 • Once daily dosing olanzapine/ Atypical antipsychotic/opioid Alkermes Schizophrenia and bipolar I disorder • Designed to provide the efficacy 6/1/21 samidorphan receptor antagonist of olanzapine while mitigating oral therapy olanzapine-associated weight gain WOMEN’S HEALTH • Estetrol is a native estrogen with selective action in tissues Estelle Mithra • It has been observed to have estetrol/drospirenone Mayne Pregnancy prevention Hormonal contraceptive 4/16/21 minimal impact on liver cells and oral therapy Pharmaceuticals metabolic pathways, as well as on coagulation parameters • Proposed for the treatment of women with heavy menstrual relugolix + estradiol bleeding associated with uterine GnRH receptor antagonist + + norethindrone Myovant Uterine fibroids fibroids 6/1/21 hormone therapy oral tablet • Oriahnn (elagolix + estradiol + norethindrone) is FDA-approved for the same indication

Biosimilar Reference Status/Estimated Biosimilar Currently Drug Name Manufacturer(s) Indication(s) Comments Drug Approval Launched? ENDOCRINOLOGY • First biosimilar application MYL-1601D Mylan BLA is under FDA review after reclassification insulin aspart Novolog Diabetes mellitus No (BsUFA date: Q2 2021) of insulin products as subcutaneous injection Biocon biologic agents HEMATOLOGY • Another biosimilar to MSB11455 BLA is under FDA review Neulasta, after Fulphila, pegfilgrastim Fresenius Kabi Neulasta Neutropenia Yes - Fulphila (BsUFA date: 3/27/21) Nyvepria, Udenyca and subcutaneous injection Ziextenzo IMMUNOLOGY • Another biosimilar to AVT02 BLA is under FDA review Humira, after Abrilada, adalimumab Alvotech Humira Rheumatoid arthritis No (BsUFA date: 9/1/21) Amjevita, Cyltezo, subcutaneous injection Hadlima, Hulio, Hyrimoz • Another biosimilar to Humira, after Abrilada, Amjevita, Cyltezo, Hadlima, Hulio, Hyrimoz; CHS-1420 BLA is under FDA review Coherus If approved, Coherus plans adalimumab Humira Rheumatoid arthritis (BsUFA date: December No BioSciences to launch this product in subcutaneous injection 2021) the U.S. on or after July 1, 2023, per the terms of an agreement with Humira manufacturer AbbVie ONCOLOGY Aybintio • Another biosimilar to Samsung Bioepis BLA is under FDA review bevacizumab Avastin Breast cancer Yes - Mvasi, Zirabev Avastin, after Mvasi and (BsUFA date: 1/30/21) intravenous infusion Merck Zirabev MYL-0401O Mylan BLA is under FDA review • Another biosimilar to bevacizumab Avastin Breast cancer (BsUFA date: 1st Half of Yes - Mvasi, Zirabev Avastin, after Mvasi and intravenous infusion Biocon 2021) Zirabev

Biosimilar Reference Status/Estimated Biosimilar Currently Drug Name Manufacturer(s) Indication(s) Comments Drug Approval Launched? Colorectal

BAT1706 Non-small cell lung • Another biosimilar to Bio-Thera BLA is under FDA review bevacizumab Avastin Cervical cancers Yes - Mvasi, Zirabev Avastin, after Mvasi and Solutions, Inc. (BsUFA date: 11/27/21) intravenous infusion Glioblastoma Zirabev Renal cell carcinoma Non-Hodgkin's lymphoma Chronic lymphocytic Riabni Amgen • Another biosimilar to rituximab-arrx Rituxan leukemia FDA-approved Yes - Ruxience, Truxima Rituxan, after Ruxience Allergan intravenous infusion Granulomatotsis with and Truxima polyangiitis Microscopic polyangiitis OPHTHALMOLOGY SB11 Macular degeneration BLA is under FDA review • Would be the first Lucentis ranibizumab Samsung Bioepis Lucentis No (BsUFA date: 9/18/21) biosimilar agent intraocular injeciton Macular edema

Recent Approvals GENERIC NAME BRAND NAME MANUFACTURER(S) MARKET LAUNCH DATE rufinamide Banzel (oral suspension) Hikma 11/04/20 abiraterone acetate Zytiga (500 mg) Mylan 12/15/20 Truvada (100 mg/150 mg, 133 mg/200 mg, emtricitabine/tenofovir disoproxil fumarate Amneal 1/20/21 167 mg/250 mg)

Sun epoprostenol sodium Veletri 1/26/21 Teva

Pipeline Agents GENERIC NAME BRAND NAME MANUFACTURER(S) ANTICIPATED LAUNCH DATE Amphastar glucagon Glucagon Mylan Q1 2021 Viatris etravirine Intelence Unknown 6/14/21 Mylan sunitinib malate Sutent 8/16/21 Viatris fingolimod Gilenya (0.25 mg) Teva 11/11/21 everolimus Zortress (1 mg) Unknown 2021 Aurobindo Cipla Mylan lopinavir/ritonavir Kaletra (tablets) 2021 Viatris Hetero Macleods Pharmaceuticals Hikma ritonavir Norvir (capsules) Mylan 2021 Viatris

Recent Approvals GENERIC NAME BRAND NAME MANUFACTURER(S) MARKET LAUNCH DATE levothyroxine sodium Tirosint Lannett 11/03/20 icosapent ethyl* Vascepa Hikma 11/05/20 micafungin sodium Mycamine Apotex 11/05/20 ethinyl estradiol/norethindrone acetate Taytulla Chemo Group 11/09/20 nitazoxanide Alinia (tablet) Rising Pharmaceuticals Inc. 11/27/20 acetaminophen Ofirmev Aurobindo 12/01/20 alvimopan Entereg Watson 12/01/20 ivermectin Sklice Taro 12/02/20 Alembic Breckenridge asenapine maleate Saphris 12/11/20 Greenstone LLC Sigmapharm Laboratories meloxicam Vivlodex Lupin 12/17/20 lubiprostone Amitiza (8 mcg, 24 mcg capsule) Par 1/04/21 Amneal Zomig (nasal spray, 2.5 mg/spray, 5 mg/ zolmitriptan Grunenthal 1/21/21 spray) Impax Pipeline Agents GENERIC NAME BRAND NAME MANUFACTURER(S) ANTICIPATED LAUNCH DATE Alkem Labs Teva Hikma droxidopa Northera 2/18/21 Zydus Tasman Pharma Sun miltefosine Impavido Unknown 3/19/21 enalapril maleate Epaned Bionpharma 4/30/21 formoterol fumarate Perforomist Teva 6/22/21 ferumoxytol Feraheme Sandoz 7/15/21 * FDA-approved only for use as an adjunct to diet to reduce triglyceride levels in adults with severe hypertriglyceridemia; current market availability is sporadic.

GENERIC NAME BRAND NAME MANUFACTURER(S) ANTICIPATED LAUNCH DATE Alkem Labs Torrent Indchemie Health Specialties Actavis nebivolol hydrochloride Bystolic 9/17/21 Teva Amerigen Pharmaceuticals Hetero Glenmark Teva arformoterol tartrate Brovana Cipla 11/09/21 Lupin Akorn Sandoz bepotastine besilate Bepreve 2021 Micro Labs Apotex Roxane Hikma posaconazole Noxafil (suspension) Sandoz 2021 Par Endo

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