Cranial Nerve Diseases

Petros begins enrollment in AI integrated Human Factors Study to optimize self-screening, continuing its efforts to make STENDRA (avanafil) the first erectile dysfunction medication to achieve OTC Status (Please see important safety information below) NEW YORK, NY / ACCESSWIRE / March 19, 2024 / Petros Pharmaceuticals, Inc. (NASDAQ:PTPI), a company focused on expanding consumer access to medication through over-the- counter (OTC) drug development programs, announces it has successfully launched its artificial intelligence (AI) tool developed as a result of its collaboration with a multi-billion-dollar software developer. The tool is being integrated into the Company's web app being used for patient self-screening, which it is testing in its recently launched Human Factors study. Fady Boctor, Petros' President and Chief Commercial Officer, commented, "The utilization of AI is a logical progression as we aim to optimize the safe administration of STENDRA (avanafil), in development for OTC availability. In addition, based on our recent interaction with the FDA on our technology approach, we believe the AI component directly addresses requests made by the Agency in order to optimize selection. Ultimately, we believe the AI will help us to gather information to ensure that the patient is appropriate to receive the drug. Importantly, we continue to believe that we have sufficient funding to achieve our development goals as well as significant near-term clinical milestones for STENDRA." The Human Factors Study, which incorporates the AI tool, is designed to assess whether the web tool developed by the company can be used safely and effectively by its intended users. Subjects will be asked to perform critical tasks with the web app without any guidance from the study staff. The study is based on applicable FDA guidance for human factors studies. The outcomes from this study will further contribute to discussions with the U.S. Food and Drug Administration (FDA) regarding the need for the Additional Condition of Nonprescription Use (ACNU) with regard to the web app and the Company's endeavors to develop STENDRA into the first erectile dysfunction medication to go OTC. About Petros Pharmaceuticals Petros Pharmaceuticals is committed to the goal of becoming a leading innovator in the emerging self-care market driving expanded access to key prescription pharmaceuticals as Over-the-Counter treatment options. Currently, Petros is pursuing increased access for its flagship prescription ED therapy, STENDRA, via potential OTC designation. If ultimately approved by the FDA for OTC access, STENDRA may be the first in its class to achieve this marketing status, also establishing company know how as a proven platform for other prospective prescription therapeutics. About the OTC Pathway The process of switching a prescription medication to over the counter (OTC) first involves the design of a Drug Facts Label (DFL) that is well understood by potential consumers. Then data must show that consumers can make an appropriate decision to use or not to use the product based only upon the information on the DFL and their personal medical history. Then consumers must demonstrate that they can properly use the product based upon the information on the DFL. To accomplish these things, the FDA ordinarily requires a consumer tested OTC DFL. This testing includes conduct of iterative Label Comprehension Studies (LCS) in the general population, Self-Selection Studies (SSS) in a population interested in using the product and in specific populations who may be harmed if they use the product, and usually one Actual Use Trial (AUT) demonstrating safe and appropriate use by consumers in a simulated OTC setting. The regulations that FDA is currently finalizing introduced Additional Conditions for Nonprescription Use (ACNU) criteria that enable correct self-selection by consumers and may expand OTC access to medications that formerly could only be available by prescription. An ACNU may be an innovative computerized tool, or the additional conditions may use other approaches that support the switch process. Important Safety Information about STENDRA® (avanafil) STENDRA® (avanafil), originally launched by Auxilium Pharmaceuticals prior to that company's sale to Endo Pharmaceuticals, is an oral phosphodiesterase 5 (PDE5) inhibitor for the treatment of erectile dysfunction. STENDRA is not for use in women or children. It is not known if STENDRA is safe and effective in women or children under 18 years of age. (A 100-mg and 200-mg tablet can be taken as early as ~15 minutes before sexual activity. STENDRA only works with sexual stimulation and should not be taken more than once a day. STENDRA can be taken with or without food; do not drink too much alcohol when taking STENDRA (for example, more than 3 glasses of wine or 3 shots of whiskey) as it can increase chances of side effects. Of people enrolled in clinical trials, 1.4%, 2.0%, and 2.0%, respectively, stopped taking STENDRA (50 mg, 100 mg, or 200 mg) due to side effects compared to 1.7% on placebo. STENDRA® was designed and developed expressly for erectile dysfunction. STENDRA is contraindicated with any form of organic nitrates, in patients with known hypersensitivity to any component of the tablet, and in patients who are using a guanylate cyclase stimulator. Patients should not use STENDRA if sexual activity is inadvisable due to cardiovascular status or any other reason. Before taking STENDRA tell your doctor if you have had any kind of heart issues including heart attack, heart failure, angina and irregular heartbeat or have elevated or low blood pressure. Use of STENDRA with alpha-blockers, other antihypertensives, or substantial amounts of alcohol (greater than 3 units) may lead to hypotension. Patients should seek emergency treatment if an erection lasts greater than 4 hours. Patients should stop STENDRA and seek medical care if a sudden loss of vision occurs in one or both eyes, which could be a sign of Non Arteritic Ischemic Optic Neuropathy (NAION). Discuss with patients the increased risk of NAION in patients with a history of NAION. Patients should stop taking STENDRA and seek prompt medical attention in the event of sudden decrease or loss of hearing. STENDRA can potentiate the hypotensive effect of nitrates, alpha blockers, antihypertensives, and alcohol. CYP3A4 inhibitors (e.g., ketoconazole, ritonavir, erythromycin) increase STENDRA exposure. For patients taking concomitant strong CYP3A4 inhibitors (including ketoconazole, ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir and telithromycin), do not use STENDRA. Combination with Other PDE5 Inhibitors or Erectile Dysfunction Therapies is not recommended. The safety of STENDRA is unknown in patients with bleeding disorders and patients with active peptic ulceration. The use of STENDRA offers no protection against sexually transmitted diseases including HIV. Consider counseling patients on protective measures for sexually transmitted diseases. The most common adverse reactions reported with use of STENDRA include headache, flushing, nasal congestion, nasopharyngitis, and back pain. For more information about STENDRA, call 844-458-4887. If you would like to report an adverse event or product complaint, please contact us at 844-458-4887. You are encouraged to report negative side effects of prescription drugs to the FDA by calling 1-800-FDA-1088, or at . Please see the full Prescribing Information and Patient Information. Cautionary Note Regarding Forward-Looking Statements This press release includes forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. These forward-looking statements are based upon Petros Pharmaceuticals, Inc.'s ("Petros," "we," "our," "us" or the "Company") management's assumptions, expectations, projections, intentions, and beliefs about future events. In some cases, predictive, future-tense or forward-looking words such as "intend," "develop," "goal," "plan," "predict", "may," "will," "project," "estimate," "anticipate," "believe," "expect," "continue," "potential," "opportunity," "forecast," "should," "target," "pursuit," "strategy" and similar expressions, whether in the negative or affirmative, that reflect our current views with respect to future events and operational, economic and financial performance are intended to identify forward-looking statements, but are not the exclusive means of identifying such statements. Such forward-looking statements are only predictions, and actual results and the timing of certain events and circumstances may differ materially from those described by the forward-looking statements as a result of risks and uncertainties, including, without limitation, Petros' ability to execute on its business strategy, including its plans to develop and commercialize its product candidates; Petros' ability to receive clearance from the FDA to sell STENDRA as an Over-the-Counter treatment; Petros' ability to comply with obligations as a public reporting company; Petros' ability to maintain compliance with the Nasdaq Stock Market's listing standards; risks related to Petros' ability to continue as a going concern; risks related to Petros' history of incurring significant losses; risks related to Petros' dependence on the commercialization of a single product, STENDRA®; and risks related to Petros' ability to obtain regulatory approvals for, or market acceptance of, any of its products or product candidates. Additional factors that could cause actual results to differ materially from the results anticipated in these forward-looking statements are contained in the Company's periodic reports and in other filings that the Company has or may file, with the U.S. Securities and Exchange Commission (the "SEC") under the headings "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations" and elsewhere. The Company cautions readers that the forward-looking statements included in this press release represent our beliefs, expectations, estimates and assumptions only as of the date of hereof and are not intended to give any assurance as to future results. New factors emerge from time to time, and it is not possible for us to predict all these factors. Further, the Company cannot assess the effect of each such factor on our business or the extent to which any factor, or combination of factors, may cause actual results to be materially different from those contained in any forward-looking statement. Accordingly, you should not unduly rely on any forward-looking statements. The Company undertakes no obligation to update or revise any forward-looking statements contained in this press release, whether as a result of new information, future events, a change in our views or expectations or otherwise, except as required by federal securities laws. Contacts Investors: CORE IR ir@petrospharma.com Media: Jules Abraham CORE IR 917-885-7378 pr@coreir.com SOURCE: Petros Pharmaceuticals, Inc. View the original press release on accesswire.com

A successful year including NASDAQ listing and positive results from two Phase 3 programs in OCS-01: Phase 3 Stage 1 DIAMOND trial for Diabetic Macular Edema (DME), and Phase 3 OPTIMIZE-1 trial for inflammation and pain following cataract surgery On-track to report topline data from OCS-02 (Licaminlimab) Phase 2b RELIEF trial in Dry Eye Disease (DED) in Q2 2024, OCS-01 Phase 3 OPTIMIZE-2 trial, and OCS-05 proof-of-concept ACUITY trial in Q4 2024 Cash, cash equivalents and short-term investments of $108.9 million funding operations and planned clinical trials, as well as advancements in DIAMOND-1 and DIAMOND-2 Phase 3 trials R&D Day held on February 28, 2024, showcasing OCS-01 DME and OCS-02 DED and their transformative treatment potentials ZUG, Switzerland and BOSTON, March 18, 2024 (GLOBE NEWSWIRE) -- Oculis Holding AG (Nasdaq: OCS) (“Oculis” or the “Company”), a global biopharmaceutical company purposefully driven to save sight and improve eye care, today announced fourth quarter and full year financial results for the period ended December 31, 2023, and an overview of the Company’s progress. Riad Sherif M.D., Chief Executive Officer of Oculis: “2023 was a remarkable milestone-rich year for Oculis. Following our listing on NASDAQ, we had two positive Phase 3 data readouts with OCS-01, the first topical candidate with compelling data in DME, and achieved a strong close of the year with the initiation of three clinical trials, including the OCS-02 Phase 2b RELIEF trial in DED. As our innovative and diversified pipeline continues to advance, we remain laser-focused on delivering our key programs: OCS-01 in DME, OCS-02 in DED and OCS-05 in Acute Optic Neuritis. We are confident and excited as we move into a catalyst-rich 2024 and look forward to updating everyone on the upcoming RELIEF trial readout planned in Q2, the second Phase 3 OPTIMIZE-2 trial readout of OCS-01 in ocular surgery in Q4, which will allow us to submit our first NDA, in addition to the ACUITY trial readout of OCS-05 in Acute Optic Neuritis, also planned in Q4. I would like to thank our exceptional team and all our partners for their great contribution but also for their commitment towards our mission to save sight and improve eye care.” Q4 2023 and Recent Highlights Advanced OCS-01, a novel high concentration preservative-free topical OPTIREACH® formulation of dexamethasone with the potential to treat both front and back of the eye indications, in three ongoing pivotal trials: In DME, following the positive topline results from Stage 1 of Phase 3 DIAMOND program, the Company announced the first patient first visit in Stage 2 of the first Phase 3 DIAMOND-1 trial and in DIAMOND-2, the second Phase 3 trial required for registration. Following the positive topline results achieved in the Phase 3 OPTIMIZE-1 trial, the Company started the second Phase 3 OPTIMIZE-2 trial of OCS-01 for the treatment of inflammation and pain following cataract surgery. Achieved a record completion of patient enrolment for the Phase 2b RELIEF trial of OCS-02 (Licaminlimab), a specifically designed ophthalmic formulation of a TNFα inhibitor, eye drop formulation specifically designed with a proprietary antibody fragment technology to treat ocular inflammation. The trial, initiated in November 2023, is evaluating the efficacy and safety of OCS-02 (Licaminlimab) vs. vehicle in signs of inflammation in DED, and is further exploring its potential unique benefit in patients with a certain genotype (i.e., single-nucleotide polymorphism, SNP, related to the TNF receptor). Hosted an R&D day on February 28, 2024, with over 100 participants that featured 10 leading experts in retina and anterior segments covering OCS-01 and OCS-02 clinical programs. Presented the Phase 3 DIAMOND Stage 1 positive results of OCS-01 in DME as late-breaking abstracts at the 23rd EURETINA Congress and at the American Academy of Ophthalmology. Upcoming Clinical Milestones In 2024, the Company is focused on advancing its innovative pipeline and planned clinical development programs including: Q2 2024 OCS-02: The Phase 2b RELIEF trial evaluating topical anti-TNFα OCS-02 (Licaminlimab) efficacy and safety in DED is on track for topline results readout in Q2 2024. Q4 2024 OCS-01: Topline results from the second Phase 3 OPTIMIZE-2 trial evaluating OCS-01 once daily eye drop for the treatment of inflammation and pain following cataract surgery are anticipated by the end of 2024. If positive, the data from this trial, together with the positive results from the first Phase 3 OPTIMIZE-1 trial, are expected to support the first NDA submission of the Company. OCS-05: A serum glucocorticoid kinase-2 (SGK-2) activator and potentially disease-modifying neuroprotective candidate is initially being developed for AON. The Phase 2a PoC ACUITY trial is designed to evaluate the safety and tolerability of a once-daily injection of OCS-05 vs. placebo for 5 days, in addition to current standard of care. The trial is on track for topline readout in the fourth quarter of 2024.The Company aims to achieve IND status for OCS-05 in the U.S. in 2024. Q4 and Full Year 2023 Financial Highlights Cash position: As of December 31, 2023, the Company had total cash, cash equivalents and short-term investments of CHF 91.7 million or $108.9 million, compared to CHF 19.8 million or $21.4 million as of December 31, 2022. The increase in cash position reflects proceeds from financing transactions completed in 2023. Based on its current development plans, cash runway is expected to fund operations into late 2025. Research and development expenses were CHF 8.0 million or $9.0 million for the three-months ended December 31, 2023, compared to CHF 6.9 million or $7.1 million in the same period in 2022. The increase was primarily due to the commencement of three clinical trials during the fourth quarter of 2023: DIAMOND-1 Stage 2, OPTIMIZE-2 and RELIEF. General and administrative expenses were CHF 4.3 million or $4.9 million for the three-months ended December 31, 2023. G&A expenses remained in-line with the same period in 2022, which was CHF 4.4 million or $4.6 million. Q4 Net loss was CHF 12.5 million or $14.1 million for the fourth quarter ended December 31, 2023, compared to CHF 9.2 million or $9.5 million in the fourth quarter of 2022. The increase in net loss was primarily driven by increases in clinical development expenses, partially offset by changes in the fair value (non-cash) adjustment of outstanding warrants. FY2023 Net loss was CHF 88.8 million or $98.8 million for the year ended December 31, 2023, or CHF 2.97 or $3.31 loss per share (basic and diluted) compared to CHF 38.7 million or $40.5 million, or CHF 11.32 or $11.86 loss per share (basic and diluted) in the year ended December 31, 2022. The increase in net loss was primarily driven by the non-recurring merger and listing expense in Q1 2023, increases in clinical development expenses, public company expenses, and the fair value (non-cash) adjustment of outstanding warrants. FY2023 Non-IFRS net loss was CHF 49.0 million or $54.5 million, or CHF 1.64 or $1.83 per share, for the year ended December 31, 2023, compared to CHF 38.7 million or $40.5 million, or CHF 11.32 or $11.86 per share, for the year ended December 31, 2022. The increase in non-IFRS net loss was primarily driven by increases in clinical development expenses, G&A expenses related to operating as a public company, and an increase in the fair value (non-cash) adjustment of outstanding warrants. Non-IFRS Financial Information This press release contains financial measures that do not comply with International Financial Reporting Standards (IFRS) including non-IFRS net loss for the full year 2023, and non-IFRS net loss per common share for the same period. These non-IFRS financial measures exclude the impact of items that the Company’s management believes affect comparability or underlying business trends. These measures supplement the Company’s financial results prepared in accordance with IFRS. The Company’s management uses these measures to better analyze its financial results and better estimate its financial outlook. In management’s opinion, these non-IFRS measures are useful to investors and other users of the Company's financial statements by providing greater transparency into the ongoing operating performance of the Company and its future outlook. Such measures should not be deemed to be an alternative to IFRS requirements. The non-IFRS measures for the reported periods reflect adjustments made to exclude: Merger and listing expense, which was a one-time and non-cash expense CHF 34.9 million or $38.2 million in the first quarter of 2023 and in the year-to-date total operating expenses. During the third quarter of 2023, the Company gave effect to the impending dissolution of its Merger Sub 2 entity pursuant to the Business Combination Agreement with EBAC, which is expected to be completed in the coming months. As a result, the cumulative translation adjustments related to Merger Sub 2 previously reported in equity and recognized in other comprehensive loss, were reclassified from equity to the Condensed Consolidated Interim Statement of Loss for the year ended December 31, 2023. The resulting non-cash foreign exchange impact of such reclassification amounted to CHF 5.0 million or $5.7 million for the year ended December 31, 2023. The non-IFRS measures presented here are also unlikely to be comparable with non-IFRS disclosures released by other companies. See the “Reconciliation of Non-IFRS Measures (Unaudited)” table below for a reconciliation of these non-IFRS measures to the most directly comparable IFRS measures. Consolidated Statements of Financial Position (Amounts in CHF thousands) As of December 31, As of December 31, 2023 2022 ASSETS Non-current assets Property and equipment, net 288 365 Intangible assets 12,206 12,206 Right-of-use assets 755 758 Other non-current assets 89 74 Total non-current assets 13,338 13,403 Current assets Other current assets 8,488 2,959 Accrued income 876 912 Short-term financial assets 53,324 - Cash and cash equivalents 38,327 19,786 Total current assets 101,015 23,657 TOTAL ASSETS 114,353 37,060 EQUITY AND LIABILITIES Shareholders' equity Share capital 366 39 Share premium 288,162 10,742 Reserve for share-based payment 6,379 2,771 Actuarial loss on post-employment benefit obligations (1,072) (264) Treasury shares - (1) Cumulative translation adjustments (327) (300) Accumulated losses (199,780) (110,978) Total equity 93,728 (97,991) Non-current liabilities Long-term lease liabilities 431 491 Long-term financial debt - 122,449 Long-term payables 378 - Defined benefit pension liabilities 728 91 Total non-current liabilities 1,537 123,031 Current liabilities Trade payables 7,596 3,867 Accrued expenses and other payables 5,948 8,011 Short-term lease liabilities 174 142 Warrant liabilities 5,370 - Total current liabilities 19,088 12,020 Total liabilities 20,625 135,051 TOTAL EQUITY AND LIABILITIES 114,353 37,060 Consolidated Statements of Loss (Amounts in CHF thousands, except per share data) For the three months ended December 31, For the years ended December 31, 2023 2022 2023 2022 Grant income 185 214 883 912 Operating income 185 214 883 912 Research and development expenses (8,029) (6,889) (29,247) (22,224) General and administrative expenses (4,340) (4,438) (17,487) (11,064) Merger and listing expense - - (34,863) - Operating expenses (12,369) (11,327) (81,597) (33,288) Operating loss (12,184) (11,113) (80,714) (32,376) Finance income 656 56 1,429 126 Finance expense (12) (1,323) (1,315) (6,442) Fair value adjustment on warrant liabilities 1,207 - (3,431) - Foreign currency exchange gain (loss), net (2,179) 3,183 (4,664) 49 Finance result, net (328) 1,916 (7,981) (6,267) Loss before tax for the period (12,512) (9,197) (88,695) (38,643) Income tax benefit (expense) 13 14 (107) (55) Loss for the period (12,499) (9,183) (88,802) (38,698) Loss per share: Basic and diluted loss attributable to equity holders (0.34) (2.62) (2.97) (11.32) Reconciliation of Non-IFRS Measures (Unaudited) (Amounts in CHF thousands, except per share data) For the years ended ended December 31, 2023 2022 2021 IFRS loss for the period (88,802) (38,698) (18,552) Non-IFRS adjustments: Merger and listing expense (i) 34,863 - - Merger Sub 2 reclassification from equity to foreign exchange loss (ii) 4,978 - - Non-IFRS loss for the period (48,961) (38,698) (18,552) IFRS basic and diluted loss attributable to equity holders (2.97) (11.32) (5.84) Non-IFRS basic and diluted loss attributable to equity holders (1.64) (11.32) (5.84) IFRS weighted-average number of shares used to compute loss per share basic and diluted 29,899,651 3,417,521 3,175,340 (i) Merger and listing expense is the difference between the fair value of the shares transferred and the fair value of the EBAC net assets per the Business Combination Agreement. This merger and listing expense is non-recurring in nature and represented a share-based payment made in exchange for a listing service and does not lead to any cash outflows. (ii) The reclassification of cumulative translation adjustments from equity to foreign exchange loss results from the impact of the impending dissolution of Merger Sub 2, which is expected to occur in the coming months. This exchange loss is non-recurring in nature and does not lead to any cash outflows. About Oculis Oculis is a global biopharmaceutical company (Nasdaq: OCS) purposefully driven to save sight and improve eye care. Oculis’ highly differentiated pipeline comprises multiple innovative product candidates in development. It includes OCS-01, a topical eye drop candidate for diabetic macular edema (DME) and for the treatment of inflammation and pain following cataract surgery; OCS-02, a topical biologic anti-TNFα eye drop candidate for dry eye disease (DED) and for non-infectious anterior uveitis; and OCS-05, a disease modifying candidate for acute optic neuritis (AON) and other neuro-ophthalmic disorders such as glaucoma, diabetic retinopathy, geographic atrophy, and neurotrophic keratitis. Headquartered in Switzerland and with operations in the U.S., Oculis’ goal is to deliver life-changing treatments to patients worldwide. The company is led by an experienced management team with a successful track record and is supported by leading international healthcare investors. For more information, please visit: Oculis Contacts Ms. Sylvia Cheung, CFO sylvia.cheung@oculis.com Investor & Media Relations LifeSci Advisors Corey Davis, Ph.D. cdavis@lifesciadvisors.com 1-212-915-2577 Cautionary Statement Regarding Forward Looking Statements This press release contains forward-looking statements and information. For example, statements regarding the potential benefits of OCS-01, OCS-02 and OCS-05, including patient impact and market opportunity; the potential of OCS-01 for treating front- and back-of-the-eye diseases; the potential for OCS-01 to become a new standard of care with the first once-daily, topical, preservative-free corticosteroid for treating inflammation and pain following ocular surgery; the potential of OCS-01 for the treatment of DME, inflammation and pain following ocular surgery and CME; the potential of OCS-02 for treating DED; the potential of OCS-02 to become the first approved topical anti- TNFα for DED; the potential of OCS-05 for treating AON and other neuro-ophthalmic disorders; expected cash runway; expected future milestones and catalysts, including the timing of completing enrolment in the RELIEF trial, topline results for OPTIMIZE-2 and ACUITY trials and IND status for OCS-05; the initiation, timing, progress and results of Oculis’ clinical and preclinical studies; Oculis’ research and development programs, regulatory and business strategy, future development plans, and management; Oculis’ ability to advance product candidates into, and successfully complete, clinical trials; and the timing or likelihood of regulatory filings and approvals, are forward-looking. All forward-looking statements are based on estimates and assumptions that, while considered reasonable by Oculis and its management, are inherently uncertain and are inherently subject to risks, variability and contingencies, many of which are beyond Oculis’ control. These forward-looking statements are provided for illustrative purposes only and are not intended to serve as, and must not be relied on by an investor as, a guarantee, assurance, prediction or definitive statement of a fact or probability. Actual events and circumstances are difficult or impossible to predict and will differ from assumptions. All forward-looking statements are subject to risks, uncertainties and other factors that may cause actual results to differ materially from those that we expected and/or those expressed or implied by such forward-looking statements. Forward-looking statements are subject to numerous conditions, many of which are beyond the control of Oculis, including those set forth in the Risk Factors section of Oculis’ annual report on Form 20-F and any other documents filed with the U.S. Securities and Exchange Commission (the “SEC”). Copies of these documents are available on the SEC’s website, Oculis undertakes no obligation to update these statements for revisions or changes after the date of this release, except as required by law.

FDA ODAC unanimously votes 11 to 0 supporting favorable risk-benefit assessment of CARVYKTI® based on results from the Phase 3 CARTITUDE-4 study RARITAN, N.J., March 15, 2024 /PRNewswire/ -- Johnson & Johnson announced today that the U.S. Food and Drug Administration (FDA) Oncologic Drugs Advisory Committee (ODAC) recommends CARVYKTI® (ciltacabtagene autoleucel, cilta-cel) for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least one prior line of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD) and who are refractory to lenalidomide. The committee reviewed survival and safety data from the Phase 3 CARTITUDE-4 study and voted unanimously in favor of CARVYKTI® (11 to 0) finding the risk-benefit assessment of CARVYKTI® for the proposed indication as favorable. A supplemental Biologics License Application (sBLA) supported by the CARTITUDE-4 study is currently under review by the FDA with a Prescription Drug User Fee Act (PDUFA) date of April 5, 2024. "We are pleased with the advisory committee's support for CARVYKTI in earlier lines of treatment based on the CARTITUDE-4 data," said Jordan Schecter, M.D., Vice President, Disease Area Leader, Multiple Myeloma, Johnson & Johnson Innovative Medicine. "As a physician and researcher committed to advancing patient care, the potential of CARVYKTI in earlier lines of therapy represents an important therapeutic option for patients with multiple myeloma." The committee reviewed data from the CARTITUDE-4 study, the first randomized Phase 3 study of CARVYKTI®, which evaluated the efficacy and safety of CARVYKTI® versus pomalidomide, bortezomib and dexamethasone (PVd) or daratumumab, pomalidomide and dexamethasone (DPd) in the treatment of patients with relapsed and lenalidomide-refractory multiple myeloma who received one to three prior lines of therapy.1 These data also served as the basis for the recent European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) positive opinion of a Type II variation for CARVYKTI® in the treatment of patients with relapsed and refractory multiple myeloma who have received at least one prior therapy, including an IMiD and a PI, and are refractory to lenalidomide.2 Results from the CARTITUDE-4 study were initially presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting and published in The New England Journal of Medicine.1,3 "Multiple myeloma is a disease with high unmet need as patients experience relapse or become refractory to treatments over time," said Sundar Jagannath, M.D., Director of the Center of Excellence for Multiple Myeloma and Professor of Medicine, Hematology and Medical Oncology, Mount Sinai.‡ "The availability of a cellular therapy like cilta-cel that can be used earlier in the treatment of this progressive disease is critically important, offering patients a chance of deep and durable responses with a one-time infusion." The ODAC is convened upon request of the FDA to review and evaluate safety and efficacy data of human drug products for use in the treatment of oncologic diseases. The committee provides non-binding recommendations based on its evaluation; however, final decisions on approval of the drug are made by the FDA. About CARVYKTI® (ciltacabtagene autoleucel; cilta-cel) CARVYKTI® received U.S. Food and Drug Administration approval in February 2022 for the treatment of adults with relapsed or refractory multiple myeloma after four or more prior lines of therapy, including a PI, an IMiD agent, and an anti-CD38 monoclonal antibody.4 In May 2022, the European Commission granted conditional marketing authorization of CARVYKTI® for the treatment of adults with relapsed and refractory multiple myeloma who have received at least three prior therapies, including an IMiD agent, a PI and an anti-CD38 antibody, and have demonstrated disease progression on the last therapy. CARVYKTI® is a BCMA-directed, genetically modified autologous T-cell immunotherapy, which involves reprogramming a patient's own T-cells with a transgene encoding chimeric antigen receptor (CAR) that directs the CAR positive T-cells to eliminate cells that express BCMA. BCMA is primarily expressed on the surface of malignant multiple myeloma B-lineage cells, as well as late-stage B cells and plasma cells. The CARVYKTI® CAR protein features two BCMA-targeting single domains designed to confer high avidity against human BCMA. Upon binding to BCMA-expressing cells, the CAR promotes T-cell activation, expansion, and elimination of target cells. In December 2017, Janssen Biotech, Inc. entered into an exclusive worldwide license and collaboration agreement with Legend Biotech USA, Inc. to develop and commercialize CARVYKTI®. For more information, visit . 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.5 In multiple myeloma, these plasma cells proliferate and spread rapidly and replace normal cells in the bone marrow with tumors.6 Multiple myeloma is the third most common blood cancer worldwide and remains an incurable disease.7 In 2024, it was estimated that more than 35,000 people will be diagnosed with multiple myeloma in the U.S. and more than 12,000 people would die from the disease.8 People living with multiple myeloma have a 5-year survival rate of 59.8 percent.9 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.10,11 CARVYKTI® IMPORTANT SAFETY INFORMATION WARNINGS AND PRECAUTIONS Cytokine Release Syndrome (CRS) including fatal or life-threatening reactions, occurred following treatment with CARVYKTI® in 95% (92/97) of patients receiving ciltacabtagene autoleucel. Grade 3 or higher CRS (2019 ASTCT grade) occurred in 5% (5/97) of patients, with Grade 5 CRS reported in 1 patient. The median time to onset of CRS was 7 days (range: 112 days). The most common manifestations of CRS included pyrexia (100%), hypotension (43%), increased aspartate aminotransferase (AST) (22%), chills (15%), increased alanine aminotransferase (ALT) (14%) and sinus tachycardia (11%). Grade 3 or higher events associated with CRS included increased AST and ALT, hyperbilirubinemia, hypotension, pyrexia, hypoxia, respiratory failure, acute kidney injury, disseminated intravascular coagulation and hemorrhage, HLH/MAS, angina pectoris, supraventricular and ventricular tachycardia, malaise, myalgias, increased C-reactive protein, ferritin, blood alkaline phosphatase and gamma-glutamyl transferase. Identify CRS based on clinical presentation. Evaluate for and treat other causes of fever, hypoxia, and hypotension. CRS has been reported to be associated with findings of HLH/MAS, and the physiology of the syndromes may overlap. HLH/MAS is a potentially life-threatening condition. In patients with progressive symptoms of CRS or refractory CRS despite treatment, evaluate for evidence of HLH/MAS. One patient with CRS and suspected HLH/MAS developed a fatal retroperitoneal hemorrhage in the setting of thrombocytopenia, coagulopathy and anticoagulation. Sixty-nine of 97 (71%) patients received tocilizumab and/or a corticosteroid for CRS after infusion of ciltacabtagene autoleucel. Forty-four (45%) patients received only tocilizumab, of whom 33 (34%) received a single dose and 11 (11%) received more than one dose; 24 patients (25%) received tocilizumab and a corticosteroid, and one patient (1%) received only corticosteroids. Ensure that a minimum of two doses of tocilizumab are available prior to infusion of CARVYKTI®. Monitor patients at least daily for 10 days following CARVYKTI® infusion at a REMS-certified healthcare facility for signs and symptoms of CRS. Monitor patients for signs or symptoms of CRS for at least 4 weeks after infusion. At the first sign of CRS, immediately institute treatment with supportive care, tocilizumab, or tocilizumab and corticosteroids. Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time. Neurologic toxicities, which may be severe, life-threatening or fatal, occurred following treatment with CARVYKTI®. Neurologic toxicities included ICANS, neurologic toxicity with signs and symptoms of parkinsonism, Guillain-Barré Syndrome, immune mediated myelitis, peripheral neuropathies, and cranial nerve palsies. Counsel patients on the signs and symptoms of these neurologic toxicities, and on the delayed nature of onset of some of these toxicities. Instruct patients to seek immediate medical attention for further assessment and management if signs or symptoms of any of these neurologic toxicities occur at any time. Overall, one or more subtypes of neurologic toxicity described below occurred following ciltacabtagene autoleucel in 26% (25/97) of patients, of which 11% (11/97) of patients experienced Grade 3 or higher events. These subtypes of neurologic toxicities were also observed in two ongoing studies. Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS): Patients may experience fatal or life-threatening ICANS following treatment with CARVYKTI®, including before CRS onset, concurrently with CRS, after CRS resolution, or in the absence of CRS. ICANS occurred in 23% (22/97) of patients receiving ciltacabtagene autoleucel including Grade 3 or 4 events in 3% (3/97) and Grade 5 (fatal) events in 2% (2/97). The median time to onset of ICANS was 8 days (range 1-28 days). All 22 patients with ICANS had CRS. The most frequent (≥5%) manifestation of ICANS included encephalopathy (23%), aphasia (8%) and headache (6%). Monitor patients at least daily for 10 days following CARVYKTI® infusion at the REMS certified healthcare facility for signs and symptoms of ICANS. Rule out other causes of ICANS symptoms. Monitor patients for signs or symptoms of ICANS for at least 4 weeks after infusion and treat promptly. Neurologic toxicity should be managed with supportive care and/or corticosteroids as needed. Parkinsonism: Of the 25 patients in the CARTITUDE-1 study experiencing any neurotoxicity, five male patients had neurologic toxicity with several signs and symptoms of parkinsonism, distinct from immune effector cell-associated neurotoxicity syndrome (ICANS). Neurologic toxicity with parkinsonism has been reported in other ongoing trials of ciltacabtagene autoleucel. Patients had parkinsonian and non-parkinsonian symptoms that included tremor, bradykinesia, involuntary movements, stereotypy, loss of spontaneous movements, masked facies, apathy, flat affect, fatigue, rigidity, psychomotor retardation, micrographia, dysgraphia, apraxia, lethargy, confusion, somnolence, loss of consciousness, delayed reflexes, hyperreflexia, memory loss, difficulty swallowing, bowel incontinence, falls, stooped posture, shuffling gait, muscle weakness and wasting, motor dysfunction, motor and sensory loss, akinetic mutism, and frontal lobe release signs. The median onset of parkinsonism in the 5 patients in CARTITUDE-1 was 43 days (range 15-108) from infusion of ciltacabtagene autoleucel. Monitor patients for signs and symptoms of parkinsonism that may be delayed in onset and managed with supportive care measures. There is limited efficacy information with medications used for the treatment of Parkinson's disease, for the improvement or resolution of parkinsonism symptoms following CARVYKTI® treatment. Guillain-Barré Syndrome: A fatal outcome following Guillain-Barré Syndrome (GBS) has occurred in another ongoing study of ciltacabtagene autoleucel despite treatment with intravenous immunoglobulin (IVIG). Symptoms reported include those consistent with Miller-Fisher variant of GBS, encephalopathy, motor weakness, speech disturbances and polyradiculoneuritis. Monitor for GBS. Evaluate patients presenting with peripheral neuropathy for GBS. Consider treatment of GBS with supportive care measures and in conjunction with immunoglobulin and plasma exchange, depending on severity of GBS. Immune Mediated Myelitis: Grade 3 myelitis has occurred 25 days following treatment in another ongoing study. Symptoms reported included hypoesthesia of the lower extremities and the lower abdomen with impaired sphincter control. Symptoms improved with the use of corticosteroids and intravenous immunoglobulin. Myelitis was ongoing at the time of death from other cause. Peripheral Neuropathy: Six patients in CARTITUDE-1 developed peripheral neuropathy. These neuropathies presented as sensory, motor or sensorimotor neuropathies. Median time of onset of symptoms was 62 days (range 4-136 days), median duration of peripheral neuropathies was 256 days (range 2-465 days) including those with ongoing neuropathy. Patients who experienced peripheral neuropathy also experienced cranial nerve palsies or GBS in other ongoing trials of ciltacabtagene autoleucel. Monitor patients for signs and symptoms of peripheral neuropathies. Cranial Nerve Palsies: Three patients (3.1%) experienced cranial nerve palsies in CARTITUDE-1. All three patients had 7th cranial nerve palsy; one patient had 5th cranial nerve palsy as well. Median time to onset was 26 days (range 21-101 days) following infusion of ciltacabtagene autoleucel. Occurrence of 3rd and 6th cranial nerve palsy, bilateral 7th cranial nerve palsy, worsening of cranial nerve palsy after improvement, and occurrence of peripheral neuropathy in patients with cranial nerve palsy have also been reported in ongoing trials of ciltacabtagene autoleucel. Monitor patients for signs and symptoms of cranial nerve palsies. Consider management with systemic corticosteroids, depending on the severity and progression of signs and symptoms. Hemophagocytic Lymphohistiocytosis (HLH)/Macrophage Activation Syndrome (MAS): Fatal HLH occurred in one patient (1%), 99 days after ciltacabtagene autoleucel. The HLH event was preceded by prolonged CRS lasting 97 days. The manifestations of HLH/MAS include hypotension, hypoxia with diffuse alveolar damage, coagulopathy, cytopenia, and multi-organ dysfunction, including renal dysfunction. One patient with Grade 4 HLH/MAS developed fatal intracerebral and gastrointestinal hemorrhage in the setting of coagulopathy and thrombocytopenia 12 days after treatment in another ongoing study. Patients who develop HLH/MAS have an increased risk of severe bleeding. Monitor hematological parameters in patients with HLH/MAS and transfuse per institutional guidelines. HLH is a life-threatening condition with a high mortality rate if not recognized and treated early. Treatment of HLH/MAS should be administered per institutional standards. CARVYKTI® REMS: Because of the risk of CRS and neurologic toxicities, CARVYKTI® is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the CARVYKTI® REMS. Further information is available at or 1-844-672-0067. Prolonged and Recurrent Cytopenias: Patients may exhibit prolonged and recurrent cytopenias following lymphodepleting chemotherapy and CARVYKTI® infusion. One patient underwent autologous stem cell therapy for hematopoietic reconstitution due to prolonged thrombocytopenia. In CARTITUDE-1, 30% (29/97) of patients experienced prolonged Grade 3 or 4 neutropenia and 41% (40/97) of patients experienced prolonged Grade 3 or 4 thrombocytopenia that had not resolved by Day 30 following ciltacabtagene autoleucel infusion. Recurrent Grade 3 or 4 neutropenia, thrombocytopenia, lymphopenia and anemia were seen in 63% (61/97), 18% (17/97), 60% (58/97), and 37% (36/97) after recovery from initial Grade 3 or 4 cytopenia following infusion. After Day 60 following ciltacabtagene autoleucel infusion, 31%, 12% and 6% of patients had a recurrence of Grade 3 or higher lymphopenia, neutropenia and thrombocytopenia, respectively, after initial recovery of their Grade 3 or 4 cytopenia. Eighty-seven percent (84/97) of patients had one, two, or three or more recurrences of Grade 3 or 4 cytopenias after initial recovery of Grade 3 or 4 cytopenia. Six and 11 patients had Grade 3 or 4 neutropenia and thrombocytopenia, respectively, at the time of death. Monitor blood counts prior to and after CARVYKTI® infusion. Manage cytopenias with growth factors and blood product transfusion support according to local institutional guidelines. Infections: CARVYKTI® should not be administered to patients with active infection or inflammatory disorders. Severe, life-threatening or fatal infections occurred in patients after CARVYKTI® infusion. Infections (all grades) occurred in 57 (59%) patients. Grade 3 or 4 infections occurred in 23% (22/97) of patients; Grade 3 or 4 infections with an unspecified pathogen occurred in 17%, viral infections in 7%, bacterial infections in 1%, and fungal infections in 1% of patients. Overall, four patients had Grade 5 infections: lung abscess (n=1), sepsis (n=2) and pneumonia (n=1). Grade 5 infections reported in other studies include bronchopulmonary aspergillosis, pneumocystis jirovecii pneumonia, and CMV colitis (with HSV-1 hepatitis). Another patient developed mycotic aneurysm due to cerebral aspergillosis and died of subarachnoid hemorrhage. Monitor patients for signs and symptoms of infection before and after CARVYKTI® infusion and treat patients appropriately. Administer prophylactic, pre-emptive and/or therapeutic antimicrobials according to the standard institutional guidelines. Febrile neutropenia was observed in 10% of patients after ciltacabtagene autoleucel infusion, and may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad-spectrum antibiotics, fluids and other supportive care, as medically indicated. In a randomized controlled study of relapsed or refractory multiple myeloma (CARTITUDE-4), patients treated with ciltacabtagene autoleucel had an increased rate of fatal COVID-19 infections compared to the standard therapy arm. Counsel patients on the importance of prevention measures. Follow institutional guidelines for the vaccination and management of immunocompromised patients with COVID-19. Viral Reactivation: Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure and death, can occur in patients with hypogammaglobulinemia. Perform screening for Cytomegalovirus (CMV), HBV, hepatitis C virus (HCV), and human immunodeficiency virus (HIV), or any other infectious agents if clinically indicated in accordance with clinical guidelines before collection of cells for manufacturing. Consider antiviral therapy to prevent viral reactivation per local institutional guidelines/clinical practice. Hypogammaglobulinemia was reported as an adverse event in 12% (12/97) of patients; laboratory IgG levels fell below 500 mg/dL after infusion in 92% (89/97) of patients. Monitor immunoglobulin levels after treatment with CARVYKTI® and administer IVIG for IgG <400 mg/dL. Manage per local institutional guidelines, including infection precautions and antibiotic or antiviral prophylaxis. Use of Live Vaccines: The safety of immunization with live viral vaccines during or following CARVYKTI® treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during CARVYKTI® treatment, and until immune recovery following treatment with CARVYKTI®. Hypersensitivity Reactions have occurred in 5% (5/97) of patients following ciltacabtagene autoleucel infusion. Serious hypersensitivity reactions, including anaphylaxis, may be due to the dimethyl sulfoxide (DMSO) in CARVYKTI®. Patients should be carefully monitored for 2 hours after infusion for signs and symptoms of severe reaction. Treat promptly and manage appropriately according to the severity of the hypersensitivity reaction. Secondary Malignancies: Patients may develop secondary malignancies. Monitor life-long for secondary malignancies. In the event that a secondary malignancy occurs, contact Janssen Biotech, Inc., at 1-800-526-7736 for reporting and to obtain instructions on collection of patient samples for testing of secondary malignancy of T cell origin. Effects on Ability to Drive and Use Machines: Due to the potential for neurologic events, including altered mental status, seizures, neurocognitive decline, or neuropathy, patients are at risk for altered or decreased consciousness or coordination in the 8 weeks following CARVYKTI® infusion. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery during this initial period, and in the event of new onset of any neurologic toxicities. ADVERSE REACTIONS The most common non-laboratory adverse reactions (incidence greater than 20%) are pyrexia, cytokine release syndrome, hypogammaglobulinemia, hypotension, musculoskeletal pain, fatigue, infections of unspecified pathogen, cough, chills, diarrhea, nausea, encephalopathy, decreased appetite, upper respiratory tract infection, headache, tachycardia, dizziness, dyspnea, edema, viral infections, coagulopathy, constipation, and vomiting. The most common laboratory adverse reactions (incidence greater than or equal to 50%) include thrombocytopenia, neutropenia, anemia, aminotransferase elevation, and hypoalbuminemia. Please read full Prescribing Information, including Boxed Warning, for CARVYKTI®. 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. ‡ Dr. Sundar Jagannath has provided consulting, advisory, and speaking services to Johnson & Johnson; he has not been paid for any media work. 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 and the potential benefits and treatment impact of CARVYKTI® (ciltacabtagene autoleucel). 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; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; 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 December 31, 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 undertake to update any forward-looking statement as a result of new information or future events or developments. 1 Dhakal, B. First phase 3 results from CARTITUDE-4: Cilta-cel versus standard of care (PVd or DPd) in lenalidomide-refractory multiple myeloma. Abstract #LBA106 [Oral Presentation]. Presented at the 2023 American Society of Clinical Oncology Annual Meeting. 2 Janssen receives positive CHMP opinion for CARVYKTI (ciltacabtagene autoleutcel; cilta-cel) for treatment in earlier lines of relapsed and refractory multiple myeloma. Johnson & Johnson Innovative Medicine. . Accessed March 2024. 3 Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma. New England Journal of Medicine. . Accessed March 2024. 4 CARVYKTI® Prescribing Information. Horsham, PA: Janssen Biotech, Inc. 5 Rajkumar SV. Multiple myeloma: 2020 update on diagnosis, risk-stratification and management. Am J Hematol. 2020;95(5):548-5672020;95(5):548-567. 6 National Cancer Institute. Plasma Cell Neoplasms. . Accessed March 2024. 7 City of Hope. Multiple Myeloma: Causes, Symptoms & Treatments. . Accessed March 2024. 8 American Cancer Society. Key Statistics About Multiple Myeloma. . Accessed March 2024. 9 SEER Explorer: An interactive website for SEER cancer statistics [Internet]. Surveillance Research Program, National Cancer Institute. . Accessed March 2024. 10 American Cancer Society. What is Multiple Myeloma? . Accessed March 2024. 11 American Cancer Society. Multiple Myeloma Early Detection, Diagnosis, and Staging. . Accessed March 2024. SOURCE Johnson & Johnson