Choroidal Effusions

51 wet AMD patients with severe disease activity (mean of 442 µm central subfield thickness & presence of retinal fluid) and high treatment burden (mean of 10 anti-VEGF injections in preceding 12 months) were randomized to high (3E10 vg/eye) or low (1E10 vg/eye) dose 4D-150 or aflibercept control regimen4D-150 was well tolerated with a favorable safety profile when evaluated through up to 48 weeks of follow-up: no significant inflammation observed (including no Grade ≥1+ inflammation in high dose patients) and all patients remained off topical steroidsHigh dose 4D-150 resulted in an 89% reduction in the annualized anti-VEGF injection rate; 84% of patients received 0 or 1 injection, and 63% were injection-free through 24 weeks; visual acuity & central subfield thickness were both stable vs. afliberceptPositive interim results enable rapid advancement towards pivotal development, with Phase 3 clinical trial initiation expected in Q1 2025Company to host webcast on Monday, February 5, 2024 at 8:00 a.m. ET EMERYVILLE, Calif., Feb. 03, 2024 (GLOBE NEWSWIRE) -- 4D Molecular Therapeutics (Nasdaq: FDMT, 4DMT or the Company), a leading clinical-stage genetic medicines company focused on unlocking the full potential of genetic medicines to treat large market diseases, today announced positive interim data from the Phase 2 PRISM clinical trial evaluating intravitreal 4D-150 in wet age-related macular degeneration (wet AMD) patients with severe disease activity and a high treatment burden. Data presented at the Angiogenesis, Exudation, and Degeneration 2024 Conference by Arshad M. Khanani, M.D., M.A., FASRS, consisted of 24-week landmark results from the randomized Phase 2 Dose Expansion cohort of the PRISM clinical trial. “We are thrilled today to announce positive interim results that strongly validate 4D-150’s potential as a safe, convenient, durable and transformational intravitreal therapeutic for wet AMD patients, with a goal of preserving vision for the longer term,” said David Kirn, M.D., Co-founder and Chief Executive Officer of 4DMT. “We believe 4D-150 has the potential to disrupt the current treatment paradigm in these patients and that these results continue to highlight the power and value of our intravitreal R100 vector invented at 4DMT. I would like to thank the patients and investigators who are participating in the PRISM trial who helped to achieve this important milestone.” “We are pleased by the robust clinical activity demonstrated in this severe disease activity patient population with high treatment burden. We believe these positive interim Phase 2 results demonstrate a differentiated product profile for the treatment of wet AMD, including in these most difficult to treat patients that have not been studied adequately in prior clinical trials,” said Robert Kim, M.D., Chief Medical Officer. “We look forward to discussions with regulators to align on a Phase 3 development plan expedited by FDA RMAT and EMA PRIME designations to advance 4D-150 with the goal of providing a compelling new treatment option for millions of patients suffering from these blinding VEGF-driven retinal diseases.” “Wet AMD is a chronic disease, and many of our patients require long-term, frequent intravitreal injections. Unfortunately, under-treatment and suboptimal disease control contribute to vision loss in the real world," said Arshad M. Khanani, M.D., M.A., FASRS, Director of Clinic Research at Sierra Eye Associates, Reno, Nevada. "I am encouraged by the potential of a one-time intravitreal injection of 4D-150 for treating wet AMD. Results from the Phase 1 and interim results from Phase 2 cohorts of the PRISM study confirm that 4D-150 is well tolerated and maintains stable visual acuity in previously treated high-need patients. 4D-150 also significantly reduces treatment burden while effectively controlling disease activity without fluid fluctuations. I believe 4D-150 has the potential to revolutionize the treatment approach for our patients with wet AMD, and I am looking forward to participating in the Phase 3 trials." Phase 2 PRISM Clinical Trial Dose Expansion Cohort Background & Summary Baseline Characteristics The Dose Expansion cohort of the PRISM study is a randomized, controlled Phase 2 clinical trial evaluating 4D-150 in previously treated wet AMD patients with severe disease activity (≥325 µm central subfield thickness (CST) measured by optical coherence tomography (OCT) and presence of subretinal or intraretinal fluid) and a high treatment burden (≥6 anti-VEGF injections in the prior 12 months). The trial enrolled 51 patients with severe disease activity and treatment burden: Mean CST: 442 µmMean anti-VEGF injections in the prior 12 months (actual): 9.6Mean time since diagnosis (years): 3.1 Enrolled patients were randomized 2:2:1 to receive a single high (3E10 vg/eye) or low (1E10 vg/eye) intravitreal dose of 4D-150 or intravitreal aflibercept 2 mg every 8 weeks (control). Phase 2 PRISM Topline Interim Results (Data cutoff: January 19, 2024) A single intravitreal dose of 4D-150 demonstrated favorable safety results through the data cutoff date (all ophthalmic exams through up to 48 weeks of follow-up): No significant intraocular inflammation High dose: None97% (38 of 39 pts) completed 20-week prophylactic topical corticosteroid taper on scheduleLow dose: Single eye at week 16 had 1+ anterior mixed (pigmented & white blood) cells, resolved by next visit and completed prophylactic topical corticosteroid taper by week 26All patients currently off steroids No 4D-150–related serious adverse events (SAEs) or study eye SAEsNo hypotony, endophthalmitis, retinal vasculitis, choroidal effusions, or retinal artery occlusions 24-week landmark analysis for key efficacy endpoints: Treatment burden reduction: 89% and 85% reduction in annualized anti-VEGF injection rates in the high (3E10 vg/eye) and low (1E10 vg/eye) 4D-150 dose arms, respectively84% and 90% of patients received 0 or 1 supplemental aflibercept injection in the high and low 4D-150 dose arms, respectively63% and 50% of patients were supplemental aflibercept injection-free in the high and low 4D-150 dose arms, respectively Visual and retina anatomic outcomes (difference in the average of week 20 & 24 adjusted mean change from baseline vs. aflibercept control arm): Best corrected visual acuity (BCVA): –1.8 and +1.8 Early Treatment Diabetic Retinopathy Study (ETDRS) letters for the 3E10 and 1E10 vg/eye 4D-150 dose arms, respectivelyCentral subfield thickness (CST): –8.3 and +29.9 µm for the 3E10 and 1E10 vg/eye 4D-150 dose arms, respectively; highlights notable reduction in retinal anatomical variability in high dose arm across all timepoints PRISM Phase 1 Long-Term Follow-Up Update (Data cutoff: January 19, 2024) Safety results maintained in all 15 patients treated to date (up to 104 weeks of follow-up) with no new inflammation and no change in steroid statusThree patients treated with high dose (3E10 vg/eye) 4D-150 were previously reported to be injection-free after 52 weeks of follow-up; all 3 patients remained injection-free through 80–104 weeks (up to 2 years) of follow-up Additional 4D-150 Program Updates 110 patients have been enrolled and dosed to date with 4D-150 in the following cohorts: PRISM Dose Exploration (N=15), Dose Expansion (N=41, excluding control arm), Population Extension (N=32), and SPECTRA Dose Confirmation (N=22) No clinically significant treatment-emergent inflammation reported Enrollment completed ahead of schedule in Phase 2 PRISM Population Extension cohort evaluating 4D-150 in wet AMD patients with broader disease severity (no minimum CST) and lower treatment burden (1-6 anti-VEGF injections in prior 12 months, ≥1 in last 12 weeks), with 32 patients dosed with 3E10 or 1E10 vg/eye of 4D-150Pivotal study planning ongoing with FDA and EMA under RMAT and PRIME designations 4DMT plans for the first Phase 3 study to be a BCVA non-inferiority study vs aflibercept 2 mg every 8 weeks; 3E10 vg/eye has been selected as study doseApplication of preliminary Phase 3 eligibility criteria for BCVA and CST to the PRISM Dose Expansion Phase 2 study (16 of 20 in high dose 4D-150 arm and 6 of 10 in aflibercept arm met criteria) demonstrated: BCVA: +3.3 letters favoring high dose 4D-150 vs. afliberceptCST: –99.0 µm favoring high dose 4D-150 vs. afliberceptAnti-VEGF treatment burden: 90% reduction in annualized injection rate (88% received 0 or 1 injection, 63% were injection-free) Enrollment and dosing completed in Phase 2 SPECTRA Part 1 Dose Confirmation cohort evaluating 4D-150 in diabetic macular edema (DME), with 22 patients dosed with 3E10 or 1E10 vg/eye of 4D-150 Upcoming 4D-150 Milestones Additional FDA and EMA interactions planned in Q2 2024, with an update expected in Q3 2024Phase 2 PRISM Population Extension cohort evaluating 4D-150 in wet AMD patients with broader disease severity: Initial interim 24-week landmark data analysis is expected in H2 2024Phase 2 SPECTRA Part 1 Dose Confirmation cohort evaluating 4D-150 in DME: Initial interim 24-week landmark data analysis is expected in H2 2024Initiation of first Phase 3 study is expected in Q1 2025 A slide presentation with detailed results can be accessed here. Corporate Webcast Details to Discuss the Results: Title:4D-150 Randomized Phase 2 Dose Expansion in Severe Disease Activity Wet AMD with High Treatment Burden: Interim Clinical Data & Program UpdateDate/Time:Monday, February 5, 2024 at 8:00 a.m. ETRegistration:Link An archived copy of the webcast will be available for up to one year by visiting the “Investors & Media” section of the 4DMT website at the following link: https://ir.4dmoleculartherapeutics.com/events. About 4D-150 for Wet AMD 4D-150 is comprised of our customized and evolved intravitreal vector, R100, and a transgene cassette that expresses both aflibercept and a VEGF-C inhibitory RNAi. This dual-transgene payload inhibits four members of the VEGF angiogenic family of factors that drive wet AMD and DME: VEGF A, B, C and PlGF. R100 was invented at 4DMT through our proprietary Therapeutic Vector Evolution platform; we developed this platform utilizing principles of directed evolution, a Nobel Prize-winning technology. 4D-150 is designed for single, low-dose intravitreal delivery for transgene expression from the retina without significant inflammation. About Wet AMD Wet AMD is a highly prevalent disease with estimated incidence rate of 200,000 new patients per year in the United States. It is estimated that the total prevalence of wet AMD in certain major markets, including the United States and the European Union (major markets), and Japan, will be greater than 4 million individuals in the next five years. Wet AMD is a type of macular degeneration where abnormal blood vessels (choroidal neovascularization or CNV) grow into the macula, the central area of the retina. As a consequence, CNV causes swelling and edema of the retina, bleeding and scarring, and causes visual distortion and reduced visual acuity. The proliferation and leakage of abnormal blood vessels is stimulated by VEGF. This process distorts and can potentially destroy central vision and may progress to blindness without treatment. About 4DMT 4DMT is a leading clinical-stage genetic medicines company focused on unlocking the full potential of genetic medicines to treat large market diseases in ophthalmology and pulmonology. 4DMT’s proprietary invention platform, Therapeutic Vector Evolution, combines the power of the Nobel Prize-winning technology, directed evolution, with approximately one billion synthetic AAV capsid-derived sequences to invent customized and evolved vectors for use in our wholly owned and partnered product candidates. Our product design, development, and manufacturing engine helps us efficiently create and advance our diverse product pipeline with the goal of revolutionizing medicine with potential curative therapies for millions of patients. Currently, 4DMT is advancing five clinical-stage and two preclinical product candidates, each tailored to address rare and large market diseases in ophthalmology, pulmonology, and cardiology. In addition, 4DMT is also advancing programs in CNS through a gene editing partnership. 4D Molecular Therapeutics™, 4DMT™, Therapeutic Vector Evolution™, and the 4DMT logo are trademarks of 4DMT. All of our product candidates are in clinical or preclinical development and have not yet been approved for marketing by the FDA or any other regulatory authority. No representation is made as to the safety or effectiveness of our product candidates for the therapeutic uses for which they are being studied. Learn more at www.4DMT.com and follow us on LinkedIn. Forward Looking Statements: This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, implied and express statements regarding the therapeutic potential, and clinical benefits of 4DMT’s product candidates, as well as the plans, announcements, and related timing for the clinical development of and regulatory interactions regarding 4D-150. The words "may," “might,” "will," "could," "would," "should," "expect," "plan," "anticipate," "intend," "believe," “expect,” "estimate," “seek,” "predict," “future,” "project," "potential," "continue," "target" and similar words or expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward looking statements in this press release are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including risks and uncertainties that are described in greater detail in the section entitled "Risk Factors" in 4D Molecular Therapeutics’ most recent Quarterly Report on Form 10-Q as well as any subsequent filings with the Securities and Exchange Commission. In addition, any forward-looking statements represent 4D Molecular Therapeutics' views only as of today and should not be relied upon as representing its views as of any subsequent date. 4D Molecular Therapeutics explicitly disclaims any obligation to update any forward-looking statements. No representations or warranties (expressed or implied) are made about the accuracy of any such forward looking statements. Contacts: Media: Katherine SmithInizio Evoke CommsKatherine.Smith@inizioevoke.com Investors: Julian PeiHead of Investor Relations and Corporate CommunicationsInvestor.Relations@4DMT.com267-644-5097

Data supporting the application showed the addition of DARZALEX FASPRO® to lenalidomide, bortezomib and dexamethasone (VRd) induction and consolidation and lenalidomide maintenance therapy reduced the risk of progression or death by 58 percent compared to standard of care If approved, the DARZALEX FASPRO®-based regimen has the potential to provide an effective quadruplet therapy for many patients with newly diagnosed multiple myeloma who are eligible for transplant RARITAN, N.J., Jan. 30, 2024 /PRNewswire/ -- Johnson & Johnson announced today the submission of a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) seeking approval of a new indication for DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) 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). This submission is supported by data from the Phase 3 PERSEUS (NCT03710603) study evaluating D-VRd induction and consolidation therapy, ASCT, and D-R maintenance therapy, compared to bortezomib, lenalidomide and dexamethasone (VRd), ASCT, and lenalidomide (R) maintenance. Results from the primary analysis showed that the study met its primary endpoint of progression-free survival (PFS), reducing the risk of disease progression or death by 58 percent (Hazard Ratio [HR], 0.42; 95 percent Confidence Interval [CI] 0.30-0.59; P<0.0001).1 Treatment with D-VRd and ASCT followed by D-R maintenance also increased the depth of response with higher rates of complete response (CR) or better, stringent complete response (sCR) and minimal residual disease (MRD) negativity compared to treatment with VRd, ASCT and R maintenance. Overall, 64 percent of patients who entered the maintenance phase in the D-VRd arm were able to discontinue treatment with DARZALEX FASPRO® after achieving a complete response or better and sustained MRD-negativity following at least two years of D-R maintenance in accordance with the protocol. The overall safety profile of D-VRd followed by D-R maintenance was consistent with the known safety profiles for DARZALEX FASPRO®, VRd and R. "We are committed to changing the course of multiple myeloma through building combination regimens such as D-VRd with complementary mechanisms of action. The DARZALEX FASPRO-based quadruplet therapy demonstrated a clinically significant reduction in the risk of progression or death for transplant-eligible, newly diagnosed patients with multiple myeloma," said Craig Tendler, M.D., Vice President, Clinical Development, Diagnostics, and Global Medical Affairs, Johnson & Johnson Innovative Medicine. "Patients are most likely to experience their deepest and most durable responses during the first line of treatment with D-VRd. This regimen has the potential to improve long-term outcomes for newly diagnosed patients and we look forward to working with the FDA on the review of this application." Data from the PERSEUS study were presented as a late-breaking oral presentation (LBA–1) at the 2023 American Society of Hematology (ASH) Annual Meeting and simultaneously published in The New England Journal of Medicine. About the PERSEUS study The PERSEUS study is being conducted in collaboration with the European Myeloma Network as the sponsor. PERSEUS is an ongoing, randomized, open-label, Phase 3 study comparing the efficacy and safety of D-VRd and ASCT followed by D-R maintenance vs VRd and ASCT followed by R maintenance in patients with transplant-eligible NDMM. The primary endpoint is PFS, and secondary endpoints include overall CR or better rate, overall MRD-negativity (in patients with CR or better), and overall survival. DARZALEX FASPRO® was discontinued after at least 24 months of D-R maintenance therapy in patients who had a CR or better and had sustained MRD–negative status for at least 12 months. The median age is 61.0 (range, 32-70) years for patients in the D-VRd arm and 59.0 (range, 31-70) years for patients in the VRd arm. The study is being conducted in 14 countries in Europe and Australia. About multiple myeloma Multiple myeloma is a blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow.2 In multiple myeloma, these malignant plasma cells proliferate and replace normal cells in the bone marrow.3 Multiple myeloma is the second most common blood cancer worldwide and remains an incurable disease.4 In 2024, it is estimated that more than 35,000 people will be diagnosed with multiple myeloma in the U.S. and more than 12,000 will die from the disease.5 People with multiple myeloma have a 5-year survival rate of 59.8 percent.5 While some people diagnosed with multiple myeloma initially have no symptoms, most patients are diagnosed due to symptoms that can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels, kidney problems or infections.6,7 About DARZALEX FASPRO® DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) received U.S. FDA approval in May 2020 and is approved for eight indications in multiple myeloma, three of which are for frontline treatment in newly diagnosed patients who are transplant eligible or ineligible.8 It is the only subcutaneous CD38-directed antibody approved to treat patients with multiple myeloma. DARZALEX FASPRO® is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme's ENHANZE® drug delivery technology. In August 2012, Janssen Biotech, Inc. and Genmab A/S entered a worldwide agreement, which granted Janssen an exclusive license to develop, manufacture and commercialize daratumumab. INDICATIONS DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) is indicated for the treatment of adult patients with multiple myeloma: In combination with bortezomib, melphalan, and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant In combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy In combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for autologous stem cell transplant In combination with pomalidomide and dexamethasone in patients who have received at least one prior line of therapy including lenalidomide and a proteasome inhibitor In combination with carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy In combination with bortezomib and dexamethasone in patients who have received at least one prior therapy As monotherapy in patients who have received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent For more information, visit . DARZALEX FASPRO® IMPORTANT SAFETY INFORMATION CONTRAINDICATIONS DARZALEX FASPRO® is contraindicated in patients with a history of severe hypersensitivity to daratumumab, hyaluronidase, or any of the components of the formulation. WARNINGS AND PRECAUTIONS Hypersensitivity and Other Administration Reactions Both systemic administration-related reactions, including severe or life-threatening reactions, and local injection-site reactions can occur with DARZALEX FASPRO®. Fatal reactions have been reported with daratumumab-containing products, including DARZALEX FASPRO®. Systemic Reactions In a pooled safety population of 898 patients with multiple myeloma (N=705) or light chain (AL) amyloidosis (N=193) who received DARZALEX FASPRO® as monotherapy or in combination, 9% of patients experienced a systemic administration-related reaction (Grade 2: 3.2%, Grade 3: 1%). Systemic administration-related reactions occurred in 8% of patients with the first injection, 0.3% with the second injection, and cumulatively 1% with subsequent injections. The median time to onset was 3.2 hours (range: 4 minutes to 3.5 days). Of the 140 systemic administration-related reactions that occurred in 77 patients, 121 (86%) occurred on the day of DARZALEX FASPRO® administration. Delayed systemic administration-related reactions have occurred in 1% of the patients. Severe reactions included hypoxia, dyspnea, hypertension, tachycardia, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma. Other signs and symptoms of systemic administration-related reactions may include respiratory symptoms, such as bronchospasm, nasal congestion, cough, throat irritation, allergic rhinitis, and wheezing, as well as anaphylactic reaction, pyrexia, chest pain, pruritus, chills, vomiting, nausea, hypotension, and blurred vision. Pre-medicate patients with histamine-1 receptor antagonist, acetaminophen, and corticosteroids. Monitor patients for systemic administration-related reactions, especially following the first and second injections. For anaphylactic reaction or life-threatening (Grade 4) administration-related reactions, immediately and permanently discontinue DARZALEX FASPRO®. Consider administering corticosteroids and other medications after the administration of DARZALEX FASPRO® depending on dosing regimen and medical history to minimize the risk of delayed (defined as occurring the day after administration) systemic administration-related reactions. Ocular adverse reactions, including acute myopia and narrowing of the anterior chamber angle due to ciliochoroidal effusions with potential for increased intraocular pressure or glaucoma, have occurred with daratumumab-containing products. If ocular symptoms occur, interrupt DARZALEX FASPRO® and seek immediate ophthalmologic evaluation prior to restarting DARZALEX FASPRO®. Local Reactions In this pooled safety population, injection-site reactions occurred in 8% of patients, including Grade 2 reactions in 0.7%. The most frequent (>1%) injection-site reaction was injection-site erythema. These local reactions occurred a median of 5 minutes (range: 0 minutes to 6.5 days) after starting administration of DARZALEX FASPRO®. Monitor for local reactions and consider symptomatic management. Neutropenia Daratumumab may increase neutropenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer's prescribing information for background therapies. Monitor patients with neutropenia for signs of infection. Consider withholding DARZALEX FASPRO® until recovery of neutrophils. In lower body weight patients receiving DARZALEX FASPRO®, higher rates of Grade 3-4 neutropenia were observed. Thrombocytopenia Daratumumab may increase thrombocytopenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer's prescribing information for background therapies. Consider withholding DARZALEX FASPRO® until recovery of platelets. Embryo-Fetal Toxicity Based on the mechanism of action, DARZALEX FASPRO® can cause fetal harm when administered to a pregnant woman. DARZALEX FASPRO® may cause depletion of fetal immune cells and decreased bone density. Advise pregnant women of the potential risk to a fetus. Advise females with reproductive potential to use effective contraception during treatment with DARZALEX FASPRO® and for 3 months after the last dose. The combination of DARZALEX FASPRO® with lenalidomide, thalidomide, or pomalidomide is contraindicated in pregnant women because lenalidomide, thalidomide, and pomalidomide may cause birth defects and death of the unborn child. Refer to the lenalidomide, thalidomide, or pomalidomide prescribing information on use during pregnancy. Interference With Serological Testing Daratumumab binds to CD38 on red blood cells (RBCs) and results in a positive indirect antiglobulin test (indirect Coombs test). Daratumumab-mediated positive indirect antiglobulin test may persist for up to 6 months after the last daratumumab administration. Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the patient's serum. The determination of a patient's ABO and Rh blood type are not impacted. Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received DARZALEX FASPRO®. Type and screen patients prior to starting DARZALEX FASPRO®. Interference With Determination of Complete Response Daratumumab is a human immunoglobulin G (IgG) kappa monoclonal antibody that can be detected on both the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in some DARZALEX FASPRO®-treated patients with IgG kappa myeloma protein. ADVERSE REACTIONS In multiple myeloma, the most common adverse reaction (≥20%) with DARZALEX FASPRO® monotherapy is upper respiratory tract infection. The most common adverse reactions with combination therapy (≥20% for any combination) include fatigue, nausea, diarrhea, dyspnea, insomnia, headache, pyrexia, cough, muscle spasms, back pain, vomiting, hypertension, upper respiratory tract infection, peripheral sensory neuropathy, constipation, pneumonia, and peripheral edema. The most common hematology laboratory abnormalities (≥40%) with DARZALEX FASPRO® are decreased leukocytes, decreased lymphocytes, decreased neutrophils, decreased platelets, and decreased hemoglobin. Please click here to see the full Prescribing Information. About Johnson & Johnson At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity. Learn more at or at . Follow us at @JanssenUS and @JNJInnovMed. Janssen Research & Development, LLC and Janssen Biotech, Inc. are both Johnson & Johnson companies. Cautions Concerning Forward-Looking Statements This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding product development of DARZALEX FASPRO®. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen Research & Development, LLC, Janssen Biotech, Inc., and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; competition, including technological advances, new products and patents attained by competitors; challenges to patents; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended January 1, 2023, including in the sections captioned "Cautionary Note Regarding Forward-Looking Statements" and "Item 1A. Risk Factors," and in Johnson & Johnson's subsequent Quarterly Reports on Form 10-Q and other filings with the Securities and Exchange Commission. Copies of these filings are available online at , or on request from Johnson & Johnson. None of Janssen Research & Development, LLC, Janssen Biotech, Inc., nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments. 1 Pieter Sonneveld, Dimopoulos MA, Boccadoro M, et al. Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. The New England Journal of Medicine. Published online December 12, 2023. doi: 2 Rajkumar SV. Multiple Myeloma: 2020 Update on Diagnosis, Risk-Stratification and Management. Am J Hematol. 2020;95(5):548-5672020;95(5):548-567. 3 National Cancer Institute. Plasma Cell Neoplasms. Accessed January 17, 2024. Available at: 4 Multiple Myeloma. City of Hope, 2022. Multiple Myeloma: Causes, Symptoms & Treatments. Accessed January 17, 2024. 5 American Cancer Society. Myeloma Cancer Statistics. Accessed January 17, 2024. Available at: 6 American Cancer Society. What is Multiple Myeloma? Accessed January 17, 2024. Available at: 7 American Cancer Society. Multiple Myeloma Early Detection, Diagnosis, and Staging. Accessed January 17, 2024. Available at: 8 DARZALEX FASPRO® Prescribing Information, November 2022. SOURCE Johnson & Johnson

DARZALEX FASPRO®-based induction, consolidation and maintenance regimen reduced risk of progression or death by 58 percent compared to standard of care regimen First presentation of data from Phase 3 PERSEUS study highlighted in late-breaking abstract session at ASH 2023 and simultaneously published in The New England Journal of Medicine SAN DIEGO, Dec. 12, 2023 /PRNewswire/ -- Johnson & Johnson announced today the first data from the Phase 3 PERSEUS study highlighting significant clinical improvement with a DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj)-based quadruplet induction, consolidation regimen and doublet maintenance regimen in the treatment of transplant-eligible (TE) newly diagnosed multiple myeloma (NDMM). The data, showing an unrivaled progression-free survival (PFS) in a Phase 3 study evaluating TE NDMM and clinically significant improvement of rates of overall complete response (CR) or better and minimal residual disease (MRD) negativity over the comparator arm, were featured as a late-breaking oral presentation at the 2023 American Society of Hematology (ASH) Annual Meeting (Abstract #LBA-1). The data were published simultaneously in The New England Journal of Medicine. The PERSEUS study, conducted in collaboration with the European Myeloma Network, found that induction and consolidation treatment with DARZALEX FASPRO® in combination with bortezomib, lenalidomide and dexamethasone (D-VRd), followed by DARZALEX FASPRO® and lenalidomide (D-R) maintenance, reduced the risk of disease progression or death by 58 percent (Hazard Ratio [HR], 0.42; 95 percent Confidence Interval [CI] 0.30-0.59; P <0.0001), compared to bortezomib, lenalidomide and dexamethasone (VRd) alone followed by lenalidomide (R) maintenance.1 The quadruplet regimen also significantly increased the depth of response compared to treatment with VRd alone, with higher rates of CR or better, stringent complete response (sCR), and MRD negativity. "The progression-free survival that was achieved in transplant-eligible patients who were treated with the daratumumab-based induction, consolidation and maintenance therapy regimen is unprecedented in a Phase 3 clinical study evaluating this patient population, but is not unexpected as these findings build on a number of studies that previously demonstrated clinical benefit with daratumumab-based regimens in this patient population," said Pieter Sonneveld, M.D., Ph.D., Professor of Hematology at the Erasmus University of Rotterdam and Chair of the Erasmus MC Cancer Institute, Rotterdam, Netherlands.‡ "The results we see across clinically relevant subgroups, including in patients who present with advanced disease or who are considered high risk, are promising for clinicians who are on the frontlines of treating patients who are newly diagnosed with this complex disease." The estimated 48-month PFS rates were 84.3 percent for D-VRd vs 67.7 percent for VRd. The consistent PFS improvement with D-VRd vs VRd was observed across most clinically relevant subgroups, including patients with International Staging System (ISS) stage III disease (HR, 0.42; 95 percent CI, 0.22-0.83) or high cytogenetic risk (HR, 0.59; 95 percent CI, 0.36-0.99). Treatment with D-VRd also resulted in deeper responses compared with VRd, including higher rates of sCR (69.3 percent vs 44.6 percent; P <0.0001), and ≥CR (87.9 percent vs 70.1 percent; P <0.0001). Overall MRD negativity rates (10–5) were higher with D-VRd vs VRd (75.2 percent vs 47.5 percent; P <0.0001). Sustained MRD-negativity rates (for ≥12 months) more than doubled with D-VRd (64.8 percent vs 29.7 percent; P <0.0001). Overall survival (OS) data are not yet mature but trending favorably for the D-VRd arm compared to VRd. "We now have evidence supporting this DARZALEX-based quadruplet induction and consolidation regimen and doublet maintenance regimen as a potential new standard of care in transplant-eligible disease, complementing data from the Phase 3 MAIA study, which firmly established a DARZALEX-based triplet therapy as standard of care in transplant-ineligible disease," said Craig Tendler, M.D., Vice President, Late Development and Global Medical Affairs, Johnson & Johnson Innovative Medicine. "We will continue to advance innovative regimens and approaches with DARZALEX to deliver on our commitment of transforming outcomes for patients with multiple myeloma." The overall safety profile of D-VRd was consistent with the known safety profiles for daratumumab and VRd. The most common (>10 percent) Grade 3/4 hematologic and non-hematologic adverse events (AE) with D-VRd vs VRd were neutropenia (62.1 percent vs 51.0 percent), thrombocytopenia (29.1 percent vs 17.3 percent), diarrhea (10.5 percent vs 7.8 percent), pneumonia (10.5 percent vs 6.1 percent) and febrile neutropenia (9.4 percent vs 10.1 percent). About the PERSEUS study The PERSEUS study is being conducted in collaboration with the European Myeloma Network as sponsor. PERSEUS is an ongoing, randomized, open-label, Phase 3 study comparing the efficacy and safety of D-VRd followed by D-R maintenance vs VRd followed by R maintenance in patients with transplant-eligible NDMM. The primary endpoint was PFS, and secondary endpoints included overall CR or better rate, overall MRD-negativity (in patients with CR or better), and overall survival. The median age is 61.0 (32-70) years for patients in the D-VRd arm and 59.0 (31-70) years for patients in the VRd arm. The study is being conducted in 14 countries in Europe and Australia. About multiple myeloma Multiple myeloma is an incurable blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow.2 In multiple myeloma, these plasma cells change, spread rapidly and replace normal cells in the bone marrow with tumors.3 Multiple myeloma is the third most common blood cancer and remains an incurable disease.4 In 2023, it is estimated that more than 35,000 people will be diagnosed with multiple myeloma in the U.S. and more than 12,000 people will die from the disease.5 People living with multiple myeloma have a 5-year survival rate of 59.8 percent.6 While some people diagnosed with multiple myeloma initially have no symptoms, most patients are diagnosed due to symptoms that can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels and kidney problems or infections.7,8 About DARZALEX FASPRO® and DARZALEX® DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) received U.S. FDA approval in May 2020 and is approved for eight indications in multiple myeloma, three of which are for frontline treatment in newly diagnosed patients who are transplant eligible or ineligible.9 It is the only subcutaneous CD38-directed antibody approved to treat patients with MM. DARZALEX FASPRO® is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme's ENHANZE® drug delivery technology. DARZALEX® (daratumumab) received U.S. FDA approval in November 2015 and is approved in eight indications, three of which are in the frontline setting, including newly diagnosed patients who are transplant eligible and ineligible.10 DARZALEX® is the first CD38-directed antibody approved to treat multiple myeloma.11 DARZALEX®-based regimens have been used in the treatment of more than 422,000 patients worldwide and more than 68,000 patients in the U.S. alone. In August 2012, Janssen Biotech, Inc. and Genmab A/S entered a worldwide agreement, which granted Janssen an exclusive license to develop, manufacture and commercialize daratumumab.  Since 2020, the National Comprehensive Cancer Network® (NCCN®) has recommended daratumumab-based combination regimens for the treatment of newly diagnosed multiple myeloma and relapsed and refractory multiple myeloma.† For newly diagnosed multiple myeloma in non-transplant candidates, the NCCN® guidelines recommend daratumumab in combination with lenalidomide and dexamethasone as a Category 1 preferred regimen; daratumumab in combination with bortezomib, melphalan, and prednisone as another recommended Category 1 regimen; and daratumumab in combination with bortezomib, cyclophosphamide, and prednisone as another recommended Category 2A regimen. For newly diagnosed multiple myeloma in transplant candidates, the NCCN® guidelines recommend daratumumab in combination with bortezomib, lenalidomide and dexamethasone as another recommended Category 2A regimen; daratumumab in combination with bortezomib, thalidomide and dexamethasone as a Category 2A regimen useful in certain circumstances; daratumumab in combination with carfilzomib, lenalidomide and dexamethasone as a Category 2A regimen useful in certain circumstances; and daratumumab in combination with cyclophosphamide, bortezomib and dexamethasone as a Category 2A regimen useful in certain circumstances. For maintenance in transplant candidates, the NCCN guidelines recommend daratumumab in combination with lenalidomide as useful in certain circumstances. In relapsed/refractory myeloma, four daratumumab regimens are listed as Category 1 preferred regimens for early relapses (1-3 prior therapies): daratumumab in combination with lenalidomide and dexamethasone; daratumumab in combination with bortezomib and dexamethasone; daratumumab in combination with carfilzomib and dexamethasone; and daratumumab in combination with pomalidomide and dexamethasone [after one prior therapy including lenalidomide and a proteasome inhibitor (PI)]. The NCCN® also recommends daratumumab in combination with cyclophosphamide, bortezomib and dexamethasone as another Category 2A regimen for early relapses (1-3 prior therapies) and as monotherapy as a Category 2A regimen useful in certain circumstances for early relapse patients after at least three prior therapies, including a PI and an immunomodulatory agent, or for patients who are double refractory to a PI and an immunomodulatory agent. For more information, visit . DARZALEX FASPRO® IMPORTANT SAFETY INFORMATION INDICATIONS DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) is indicated for the treatment of adult patients with multiple myeloma: In combination with bortezomib, melphalan, and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant In combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy In combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for autologous stem cell transplant In combination with pomalidomide and dexamethasone in patients who have received at least one prior line of therapy including lenalidomide and a proteasome inhibitor In combination with carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy In combination with bortezomib and dexamethasone in patients who have received at least one prior therapy As monotherapy in patients who have received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent CONTRAINDICATIONS DARZALEX FASPRO® is contraindicated in patients with a history of severe hypersensitivity to daratumumab, hyaluronidase, or any of the components of the formulation. WARNINGS AND PRECAUTIONS Hypersensitivity and Other Administration Reactions Both systemic administration-related reactions, including severe or life-threatening reactions, and local injection-site reactions can occur with DARZALEX FASPRO®. Fatal reactions have been reported with daratumumab-containing products, including DARZALEX FASPRO®. Systemic Reactions In a pooled safety population of 898 patients with multiple myeloma (N=705) or light chain (AL) amyloidosis (N=193) who received DARZALEX FASPRO® as monotherapy or in combination, 9% of patients experienced a systemic administration-related reaction (Grade 2: 3.2%, Grade 3: 1%). Systemic administration-related reactions occurred in 8% of patients with the first injection, 0.3% with the second injection, and cumulatively 1% with subsequent injections. The median time to onset was 3.2 hours (range: 4 minutes to 3.5 days). Of the 140 systemic administration-related reactions that occurred in 77 patients, 121 (86%) occurred on the day of DARZALEX FASPRO® administration. Delayed systemic administration-related reactions have occurred in 1% of the patients. Severe reactions included hypoxia, dyspnea, hypertension, tachycardia, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma. Other signs and symptoms of systemic administration-related reactions may include respiratory symptoms, such as bronchospasm, nasal congestion, cough, throat irritation, allergic rhinitis, and wheezing, as well as anaphylactic reaction, pyrexia, chest pain, pruritus, chills, vomiting, nausea, hypotension, and blurred vision. Pre-medicate patients with histamine-1 receptor antagonist, acetaminophen, and corticosteroids. Monitor patients for systemic administration-related reactions, especially following the first and second injections. For anaphylactic reaction or life-threatening (Grade 4) administration-related reactions, immediately and permanently discontinue DARZALEX FASPRO®. Consider administering corticosteroids and other medications after the administration of DARZALEX FASPRO® depending on dosing regimen and medical history to minimize the risk of delayed (defined as occurring the day after administration) systemic administration-related reactions. Ocular adverse reactions, including acute myopia and narrowing of the anterior chamber angle due to ciliochoroidal effusions with potential for increased intraocular pressure or glaucoma, have occurred with daratumumab-containing products. If ocular symptoms occur, interrupt DARZALEX FASPRO® and seek immediate ophthalmologic evaluation prior to restarting DARZALEX FASPRO®. Local Reactions In this pooled safety population, injection-site reactions occurred in 8% of patients, including Grade 2 reactions in 0.7%. The most frequent (>1%) injection-site reaction was injection-site erythema. These local reactions occurred a median of 5 minutes (range: 0 minutes to 6.5 days) after starting administration of DARZALEX FASPRO®. Monitor for local reactions and consider symptomatic management. Neutropenia Daratumumab may increase neutropenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer's prescribing information for background therapies. Monitor patients with neutropenia for signs of infection. Consider withholding DARZALEX FASPRO® until recovery of neutrophils. In lower body weight patients receiving DARZALEX FASPRO®, higher rates of Grade 3-4 neutropenia were observed. Thrombocytopenia Daratumumab may increase thrombocytopenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer's prescribing information for background therapies. Consider withholding DARZALEX FASPRO® until recovery of platelets. Embryo-Fetal Toxicity Based on the mechanism of action, DARZALEX FASPRO® can cause fetal harm when administered to a pregnant woman. DARZALEX FASPRO® may cause depletion of fetal immune cells and decreased bone density. Advise pregnant women of the potential risk to a fetus. Advise females with reproductive potential to use effective contraception during treatment with DARZALEX FASPRO® and for 3 months after the last dose. The combination of DARZALEX FASPRO® with lenalidomide, thalidomide, or pomalidomide is contraindicated in pregnant women because lenalidomide, thalidomide, and pomalidomide may cause birth defects and death of the unborn child. Refer to the lenalidomide, thalidomide, or pomalidomide prescribing information on use during pregnancy. Interference with Serological Testing Daratumumab binds to CD38 on red blood cells (RBCs) and results in a positive indirect antiglobulin test (indirect Coombs test). Daratumumab-mediated positive indirect antiglobulin test may persist for up to 6 months after the last daratumumab administration. Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the patient's serum. The determination of a patient's ABO and Rh blood type are not impacted. Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received DARZALEX FASPRO®. Type and screen patients prior to starting DARZALEX FASPRO®. Interference With Determination of Complete Response Daratumumab is a human immunoglobulin G (IgG) kappa monoclonal antibody that can be detected on both the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in some DARZALEX FASPRO®-treated patients with IgG kappa myeloma protein. ADVERSE REACTIONS In multiple myeloma, the most common adverse reaction (≥20%) with DARZALEX FASPRO® monotherapy is upper respiratory tract infection. The most common adverse reactions with combination therapy (≥20% for any combination) include fatigue, nausea, diarrhea, dyspnea, insomnia, headache, pyrexia, cough, muscle spasms, back pain, vomiting, hypertension, upper respiratory tract infection, peripheral sensory neuropathy, constipation, pneumonia, and peripheral edema. The most common hematology laboratory abnormalities (≥40%) with DARZALEX FASPRO® are decreased leukocytes, decreased lymphocytes, decreased neutrophils, decreased platelets, and decreased hemoglobin. Please click here to see the full Prescribing Information. About Johnson & Johnson At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity. Learn more at or at . Follow us at @JanssenUS and @JNJInnovMed. Janssen Research & Development, LLC and Janssen Biotech, Inc. are both Johnson & Johnson companies. Cautions Concerning Forward-Looking Statements This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding product development of DARZALEX FASPRO®. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen Research & Development, LLC, Janssen Biotech, Inc., and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; competition, including technological advances, new products and patents attained by competitors; challenges to patents; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended January 1, 2023, including in the sections captioned "Cautionary Note Regarding Forward-Looking Statements" and "Item 1A. Risk Factors," and in Johnson & Johnson's subsequent Quarterly Reports on Form 10-Q and other filings with the Securities and Exchange Commission. Copies of these filings are available online at , or on request from Johnson & Johnson. None of Janssen Research & Development, Janssen Biotech, Inc., nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments. ‡ Prof. Sonneveld has provided consulting, advisory, and speaking services to Johnson and Johnson; he has not been paid for any media work. †See the NCCN Guidelines for detailed recommendations, including other treatment options. 1 Sonneveld P et al. Phase 3 randomized study of daratumumab (DARA) + bortezomib, lenalidomide, and dexamethasone (D-VRd) versus VRd alone in patients (Pts) with newly diagnosed multiple myeloma (NDMM) who are eligible for autologous stem cell transplantation (ASCT): primary results of the PERSEUS trial. 2023 ASH Annual Meeting – American Society of Hematology. December 2023. 2 Rajkumar SV. Multiple myeloma: 2020 update on diagnosis, risk-stratification and management. Am J Hematol. 2020;95(5):548-5672020;95(5):548-567. 3 National Cancer Institute. Plasma Cell Neoplasms. Accessed July 9, 2023. Available at: 4 Multiple myeloma. City of Hope, 2022. Multiple Myeloma: Causes, Symptoms & Treatments. Accessed July 18, 2023. 5 American Cancer Society. Key Statistics About Multiple Myeloma. Accessed July 9, 2023. Available at: 6 SEER Explorer: An interactive website for SEER cancer statistics [Internet]. Surveillance Research Program, National Cancer Institute. Accessed June 30, 2023. 7 American Cancer Society. What is Multiple Myeloma? Accessed July 9, 2023. Available at: 8 American Cancer Society. Multiple Myeloma Early Detection, Diagnosis, and Staging. Accessed July 19, 2023. Available at: 9 DARZALEX FASPRO® Prescribing Information, November 2022. 10 DARZALEX® Prescribing Information, January 2023. 11 ClinicalTrials.gov Identifier NCT02076009. . Accessed October 19, 2023. SOURCE Johnson & Johnson