A Phase I/II Study of Interstitial Photodynamic Therapy Following Palliative Radiotherapy for Patients With Inoperable Malignant Central Airway Obstruction

This phase I/II trial studies the side effects of interstitial photodynamic therapy following palliative radiotherapy and how well it works in treating patients with inoperable malignant central airway obstruction. Patients who have advanced stage cancer tumors in the lung can often have the breathing passages to the lung partially or completely blocked. These tumors could be due to lung cancer or other cancers (e.g., renal, breast, kidney, etc.) that spread to the lung. This blockage puts the patient at a higher risk for respiratory failure, post-obstructive pneumonia, and prolonged hospitalizations. Treatment for these patients may include bronchoscopic intervention (such as mechanical removal, stenting, laser cauterization, or ballooning), radiation therapy with and without chemotherapy. While palliative x-ray radiotherapy may help in shrinking the tumor, high dose curative radiotherapy that can ablate (a localized, nonsurgical destruction) the tumor also has high risk to cause significant toxicity, including bleeding, abnormal connections or passageways between organs or vessels and abnormal scar tissue that can also produce airway obstruction. Photodynamic therapy (PDT) is another possible treatment that can provide local control of the tumor. PDT consists of injecting a light sensitive drug (photosensitizer, PS) into the vein, waiting for the PS to accumulate in the tumor, and then activating it with a red laser light. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Giving interstitial photodynamic therapy following palliative radiotherapy may improve tumor response and survival without the serious side effects that are associated with the typical high dose curative x-ray radiotherapy alone in patients with malignant central airway obstruction.

Start Date01 Jul 2024

Sponsor / Collaborator

Roswell Park Comprehensive Cancer Center

NCT06381154 / Not yet recruitingPhase 2

Photodynamic Priming to Facilitate Immunologic Activity of Anti-PD1 in Patients With Pancreatic Cancer

This phase II trial tests how well photoradiation with verteporfin and pembrolizumab plus standard of care chemotherapy works in treating patients with pancreatic cancer that cannot be removed by surgery (unresectable), that has spread to nearby tissue or lymph nodes (locally advanced) or to other places in the body (metastatic). Photoradiation uses light activated drugs, such as verteporfin, that become active when exposed to light. These activated drugs may kill tumor cells. Vertoporfin may also increase tumor response to immunotherapy. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as modified fluorouracil, leucovorin, irinotecan, and oxaliplatin (mFOLFIRINOX), work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Photoradiation with verteporfin and pembrolizumab plus standard of care chemotherapy may kill more tumor cells in patients with unresectable, locally advanced or metastatic pancreatic cancer.

Start Date30 Jun 2024

Sponsor / Collaborator

Mayo Clinic

[+1]

NCT04075136 / WithdrawnPhase 4IIT

OCTA-Directed PDT Triple Therapy for Treatment-Naïve Patients With Exudative Age-Related Macular Degeneration Versus Standard of Care Anti-VEGF(Anti-vascular Endothelial Growth Factor) Monotherapy

Optical Coherent Tomography Angiography (OCTA)-Directed PDT Triple Therapy for Treatment-Naïve Patients with Exudative Age-related Macular Degeneration (ARMD) versus Standard of Care Anti-VEGF Monotherapy

Start Date30 Mar 2023

Sponsor / Collaborator

Wake Forest School of Medicine

[+1]

100 Clinical Results associated with Verteporfin

100 Translational Medicine associated with Verteporfin

100 Patents (Medical) associated with Verteporfin

2,138

Literatures (Medical) associated with Verteporfin

05 Jul 2106·Oncotarget

Pharmacological activation of FOXO3 suppresses triple-negative breast cancer in vitro and in vivo

Article

Author: Chung, Young Min ; Park, See-Hyoung ; Berek, Jonathan S. ; Yang, Qin ; Ma, Jessica ; Hu, Mickey C-T.

Triple-negative breast cancer (TNBC) is the most lethal form of breast cancer. Lacking effective therapeutic options hinders treatment of TNBC. Here, we show that bepridil (BPD) and trifluoperazine (TFP), which are FDA-approved drugs for treatment of schizophrenia and angina respectively, inhibit Akt-pS473 phosphorylation and promote FOXO3 nuclear localization and activation in TNBC cells. BPD and TFP inhibit survival and proliferation in TNBC cells and suppress the growth of TNBC tumors, whereas silencing FOXO3 reduces the BPD- and TFP-mediated suppression of survival in TNBC cells. While BPD and TFP decrease the expression of oncogenic c-Myc, KLF5, and dopamine receptor DRD2 in TNBC cells, silencing FOXO3 diminishes BPD- and TFP-mediated repression of the expression of these proteins in TNBC cells. Since c-Myc, KLF5, and DRD2 have been suggested to increase cancer stem cell-like populations in various tumors, reducing these proteins in response to BPD and TFP suggests a novel FOXO3-dependent mechanism underlying BPD- and TFP-induced apoptosis in TNBC cells.

01 May 2024·Ophthalmology science

Evaluation of Verteporfin as a Novel Antifibrotic Agent in a Rabbit Model of Glaucoma Filtration Surgery

Article

Author: Singh, Kuldev ; Xia, Xin ; Dalal, Roopa ; Lin, Jonathan H ; Cotton, Renee M ; Goldberg, Jeffrey L ; Sun, Michelle T ; Charoenkijkajorn, Chaow ; Liu, Wendy W ; Garcia-Sanchez, Julian

Purpose:

Verteporfin is a benzoporphyrin derivative which is Food and Drug Administration-approved for treatment of choroidal neovascularization in conjunction with photodynamic therapy. It has been shown to prevent fibrosis and scar formation in several organs and represents a promising novel antifibrotic agent for glaucoma surgery. The goal of this study is to determine the effect of verteporfin on wound healing after glaucoma filtration surgery.

Design:

Preclinical study using a rabbit model of glaucoma filtration surgery.

Subjects:

Eight New Zealand white rabbits underwent glaucoma filtration surgery in both eyes.

Methods:

Eyes were randomized into 4 study groups to receive a postoperative subconjunctival injection of 1 mg/mL verteporfin (n = 4), 0.4 mg/mL mitomycin C (MMC; n = 4), 0.4 mg/mL MMC + 1 mg/mL verteporfin (n = 4), or balanced salt solution (BSS) control (n = 4). Bleb survival, vascularity, and morphology were graded using a standard scale over a 30-day period, and intraocular pressure (IOP) was monitored. At 30 days postoperative or surgical failure, histology was performed to evaluate for inflammation, local toxicity, and scarring.

Main Outcome Measures:

The primary outcome measure was bleb survival. Secondary outcome measures were IOP, bleb morphology, and bleb histology.

Results:

Compared to BSS control blebs, verteporfin-treated blebs demonstrated a trend toward increased surgical survival (mean 9.8 vs. 7.3 days, log rank P = 0.08). Mitomycin C-treated blebs survived significantly longer than verteporfin-treated blebs (log rank P = 0.009), with all but 1 MMC-treated bleb still surviving at postoperative day 30. There were no significant differences in survival between blebs treated with combination verteporfin + MMC and MMC alone. Mitomycin C-treated blebs were less vascular than verteporfin-treated blebs (mean vascularity score 0.3 ± 0.5 for MMC vs. 1.0 ± 0.0 for verteporfin, P < 0.01). Bleb histology did not reveal any significant toxicity in verteporfin-treated eyes. There were no significant differences in inflammation or scarring across groups.

Conclusions:

Although verteporfin remained inferior to MMC with regard to surgical survival, there was a trend toward increased survival compared with BSS control and it had an excellent safety profile. Further studies with variations in verteporfin dosage and/or application frequency are needed to assess whether this may be a useful adjunct to glaucoma surgery.

Financial Disclosures:

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

01 Feb 2024·Free radical biology & medicine

Verteporfin induces lipid peroxidation and ferroptosis in pancreatic cancer cells

Article

Author: Elmadbouh, Omer Hany Miligy ; Edderkaoui, Mouad ; Zhou, Wei ; Urrutia, Raul ; Liu, Tao ; Wang, Qiang ; Mathison, Angela J ; Osipov, Arsen ; Pandol, Stephen J ; Lim, Adrian

Pancreatic ductal adenocarcinoma (PDAC) has extremely poor prognosis, with a 5-year survival rate of approximately 11 %. Yes-associated protein (YAP) is a major downstream effector of the Hippo-YAP pathway and plays a pivotal role in regulation of cell proliferation and organ regeneration and tumorigenesis. Activation of YAP signaling has been associated with PDAC progression and drug resistance. Verteporfin (VP) is a photosensitizer used for photodynamic therapy and previous work showed that it can function as a YAP inhibitor. The efficacy of VP on human cancer are being tested in several trials. In this study, we examined the effect of VP on reactive oxygen species (ROS) and lipid peroxidation in pancreatic cancer cells, by using fluorescent molecular probes and by measuring the levels of malondialdehyde, a metabolic byproduct and marker of lipid peroxidation. We found that VP causes rapid increase of both overall ROS and lipid peroxide levels, independent of light activation. These effects were not dependent on YAP, as knockdown of YAP did not cause ROS or lipid peroxidation or enhance VP-induced ROS production. Temoporfin, another photodynamic drug, did not show similar activities. In addition, VP treatment led to loss of cell membrane integrity and reduction of viability. Notably, the activity of VP to induce lipid peroxidation was neutralized by ferroptosis inhibitors ferrostatin-1 or liproxstatin-1. VP treatment also reduced the levels of glutathione peroxidase 4 (GPX4), an enzyme that protects against lipid peroxidation. These results indicate that VP can induce lipid peroxidation and ferroptosis in the absence of light activation. Our findings reveal a novel mechanism by which VP inhibits tumor growth and provide insights into development of new therapeutic strategies for the treatment of pancreatic cancer.

News (Medical) associated with Verteporfin

01 Nov 2023

·www.globenewswire.com

Research Funded by Bay Area Lyme Foundation Identifies New Investigational Therapy Regimen Capable of Irreversibly Damaging Lyme Bacteria in Laboratory Tests

Inspired by research that targets cancer tumors, these new findings in Lyme could also lead to novel R&D strategies for other diseasesPORTOLA VALLEY, Calif., Nov. 01, 2023 (GLOBE NEWSWIRE) -- Bay Area Lyme Foundation, a leading sponsor of Lyme disease research in the US, today announced the development of a potential new drug, HS-291, that targets and destroys Borrelia burgdorferi, the bacterium that causes Lyme disease. Published in the peer-reviewed journal Cell Chemical Biology, this laboratory study represents a novel paradigm shift for anti-microbial treatment research as it is the first to target and inhibit Borrelia burgdorferi HtpG (high temperature protein G), a specific type of enzyme within the bacteria that causes Lyme disease— a condition affecting nearly 500,000 new patients annually. The research was conducted at Duke University School of Medicine, with collaboration from University of North Carolina, Tulane University, and Stanford University, and HS-291 is currently in preclinical stage testing at UC Davis. “As Lyme disease is currently treated with broad spectrum antibiotics and there are no targeted treatments, we are particularly excited about this discovery, and hopeful that our novel Lyme disease therapeutic HS-291 will specifically destroy the Lyme bacterium without off-target effects or antibiotic resistance,” said Timothy Haystead, PhD, professor of Pharmacology and Cancer Biology, Duke University School of Medicine, Bay Area Lyme Foundation grantee, and co-lead author. “This research has been an incredible opportunity to leverage knowledge from oncology to Lyme disease in order to design an investigational therapeutic that could one day benefit hundreds of thousands of patients with Lyme.” This new discovery has implications beyond Lyme disease as it demonstrates that using the drug HS-291 to deliver cellular toxins to HtpG, a type of non-essential enzyme that assists the folding or unfolding of large and complex proteins, greatly expands what can be considered druggable within any pathogen and opens a whole new area of infectious disease research. When activated, HS-291, an inhibitor of HtpG tethered to the photoactive cellular toxin verteporfin, causes discrete protein modifications, which wreaks havoc on the Lyme disease bacterium’s DNA. This impacts multiple processes including nucleoid collapse and cell wall disruptions. A single dose of HS-291, when activated by light, irreversibly damages Borrelia proteins in close proximity of Bb HtpG in vitro. “Antibiotics used to treat Lyme disease do not always work for all patients, which causes many to suffer for years with extreme symptoms including neurocognitive issues, disabling fatigue and sleep disruption,” said Linda Giampa, executive director of the Bay Area Lyme Foundation. “Bay Area Lyme concentrates on funding innovative research, including projects where knowledge can be deployed from other areas of medicine. We hope that this discovery will inspire others to join us in investing in impactful, translational research to bring relief to patients.” This research was made possible by a 2020 Bay Area Lyme Foundation grant of more than $2 million to Duke University School of Medicine in honor of Neil Spector, MD, a renowned oncologist who passed away from complications of Lyme disease that had been misdiagnosed for years. He encouraged scientists to take cancer staging techniques and immunotherapy learnings from oncology and apply them to Lyme research. Dr. Spector was the Sandra Coates associate professor in the Duke University Department of Medicine and also served on Bay Area Lyme Foundation’s Scientific Advisory Board. Haystead and Spector joined forces as Spector sought to leverage his knowledge of oncology to help better understand Lyme disease, and Haystead’s research is focused on the use of chemical biology approaches to define novel drug targets focused on the treatment of hypertension, obesity, cancer, inflammatory and infectious disease. Bay Area Lyme Foundation also funded University of North Carolina collaborator, Matt Redinbo, PhD’s research on HS-291; his lab’s crystallography work was instrumental in the discovery process. Bay Area Lyme Foundation’s research grant program was made possible by the support from the Fairbairn Family, the Younger Family Fund, and Project Lyme. About Lyme disease The most common vector-borne infectious disease in the US, Lyme disease is a potentially disabling infection caused by bacteria transmitted through the bite of an infected tick to people and pets, and may also be passed from a pregnant mother to her unborn baby. If caught early, most cases of Lyme disease can be effectively treated, but it is commonly misdiagnosed due to lack of awareness and inaccurate diagnostic tests. There are approximately 500,000 new cases of Lyme disease each year, according to statistics released in 2018 by the CDC. As a result of the difficulty in diagnosing and treating Lyme disease, up to two million Americans may be suffering from the impact of its debilitating long-term symptoms and complications, according to Bay Area Lyme Foundation estimates. About Bay Area Lyme Foundation Bay Area Lyme Foundation, a national organization committed to making Lyme disease easy to diagnose and simple to cure, is the leading public not-for-profit sponsor of innovative Lyme disease research in the US. A 501c3 organization based in Silicon Valley, Bay Area Lyme Foundation collaborates with world-class scientists and institutions to accelerate medical breakthroughs for Lyme disease. It is also dedicated to providing reliable, fact-based information so that prevention and the importance of early treatment are common knowledge. A pivotal donation from The LaureL STEM FUND covers overhead costs and allows for 100% of all donor contributions to the Bay Area Lyme Foundation to go directly to research and prevention programs. For more information about Lyme disease or to get involved, visit www.bayarealyme.org or call us at 650-530-2439. Media contact:Tara DiMiliaPhone: 908-369-7168Tara.DiMilia@tmstrat.com

04 Oct 2023

·www.biospace.com

CIMERLI® (ranibizumab-eqrn) Sales Exceed 100,000 Doses in First Year of Launch

CIMERLI® is the #1 ranibizumab biosimilar with 25% ranibizumab market share* Demonstrated safety and efficacy in clinical trials and real-world settings Robust and reliable supply addresses market need and expands anti-VEGF options across the retinal market REDWOOD CITY, Calif., Oct. 04, 2023 (GLOBE NEWSWIRE) -- Coherus BioSciences, Inc. (Coherus, Nasdaq: CHRS), today announced that sales of CIMERLI® (ranibizumab-eqrn) to retinal specialists have exceeded 100,000 doses since commercial launch on October 3, 2022. CIMERLI® is the first and only FDA-approved biosimilar interchangeable with Lucentis® for all approved indications. In August 2023, CIMERLI® achieved 25% market share of the ranibizumab market*, making it the #1 ranibizumab biosimilar. “Eclipsing 100,000 doses sold to retinal specialists within the first full year after commercial launch is an important milestone for CIMERLI® and reinforces the retinal community’s desire for a safe and effective biosimilar option to LUCENTIS®,” said Paul Reider, Chief Commercial Officer of Coherus. “Achieving 25% market share speaks to the strength of our commercial capabilities and replicates the success we saw with UDENYCA® in its first year on the market. We look forward to potential continued sales growth for CIMERLI® as more accounts continue their conversion.” “Over the past twelve months we have launched three new products: CIMERLI®, the UDENYCA® auto-injector and YUSIMRY™. We now look forward to the potential approvals of two more products this year: toripalimab for nasopharyngeal carcinoma and the UDENYCA® on-body injector, and their subsequent launches,” said Denny Lanfear, Chairman and Chief Executive Officer of Coherus. Coherus plans to report CIMERLI® net sales for the third quarter when the company reports Q3 2023 financial results in November. About CIMERLI® CIMERLI® (ranibizumab-eqrn) is the only FDA-approved biosimilar interchangeable with Lucentis® for all Lucentis® FDA-approved indications. Formerly CHS-201 (also known as FYB201), it is a biosimilar to the reference product, U.S.-licensed Lucentis®. CIMERLI® has the same product attributes as Lucentis®, in terms of dosage strengths (0.3 mg, 0.5 mg), formulation and excipients, and amino acid sequence. CIMERLI® was approved by the FDA on August 2, 2022. Coherus owns the biologics license application (BLA) for CIMERLI® and commercial rights in the U.S. and its territories. Coherus licensed CIMERLI® from Bioeq AG, a joint venture between Polpharma Biologics Group B.V. and Formycon AG. *IQVIA NSP Data August 2023. 1. CIMERLI® (ranibizumab-eqrn) U.S. Prescribing Information, August 2022. IMPORTANT SAFETY INFORMATION & INDICATIONS CIMERLI® (ranibizumab-eqrn) is interchangeable* to Lucentis® (ranibizumab injection) CIMERLI® (ranibizumab-eqrn), a vascular endothelial growth factor (VEGF) inhibitor, is indicated for the treatment of patients with: Neovascular (Wet) Age-Related Macular Degeneration (AMD) Macular Edema Following Retinal Vein Occlusion (RVO) Diabetic Macular Edema (DME) Diabetic Retinopathy (DR) Myopic Choroidal Neovascularization (mCNV) CONTRAINDICATIONS CIMERLI® is contraindicated in patients with ocular or periocular infections or known hypersensitivity to ranibizumab products or any of the excipients in CIMERLI®. Hypersensitivity reactions may manifest as severe intraocular inflammation WARNINGS AND PRECAUTIONS Endophthalmitis and Retinal Detachments: Intravitreal injections, including those with ranibizumab products, have been associated with endophthalmitis and retinal detachments. Proper aseptic injection technique should always be utilized when administering CIMERLI®. Patients should be monitored following the injection to permit early treatment, should an infection occur Increases in Intraocular Pressure: Increases in intraocular pressure (IOP) have been noted both pre-injection and post-injection (at 60 minutes) with ranibizumab products. Monitor intraocular pressure prior to and following intravitreal injection with CIMERLI® and manage appropriately Thromboembolic Events: Although there was a low rate of arterial thromboembolic events (ATEs) observed in the ranibizumab clinical trials, there is a potential risk of ATEs following intravitreal use of VEGF inhibitors. ATEs are defined as nonfatal stroke, nonfatal myocardial infarction, or vascular death (including deaths of unknown cause) Neovascular (wet) age-related macular degeneration The ATE rate in the 3 controlled neovascular AMD studies during the first year was 1.9% (17 of 874) in the combined group of patients treated with 0.3 mg or 0.5 mg ranibizumab compared with 1.1% (5 of 441) in patients from the control arms. In the second year of Studies AMD-1 and AMD-2, the ATE rate was 2.6% (19 of 721) in the combined group of ranibizumab-treated patients compared with 2.9% (10 of 344) in patients from the control arms. In Study AMD-4, the ATE rates observed in the 0.5 mg arms during the first and second year were similar to rates observed in Studies AMD-1, AMD-2, and AMD-3 In a pooled analysis of 2-year controlled studies (AMD-1, AMD-2, and a study of ranibizumab used adjunctively with verteporfin photodynamic therapy), the stroke rate (including both ischemic and hemorrhagic stroke) was 2.7% (13 of 484) in patients treated with 0.5 mg ranibizumab compared to 1.1% (5 of 435) in patients in the control arms (odds ratio 2.2 [95% confidence interval (0.8-7.1)]) Macular edema following retinal vein occlusion The ATE rate in the 2 controlled RVO studies during the first 6 months was 0.8% in both the ranibizumab and control arms of the studies (4 of 525 in the combined group of patients treated with 0.3 mg or 0.5 mg ranibizumab and 2 of 260 in the control arms). The stroke rate was 0.2% (1 of 525) in the combined group of ranibizumab-treated patients compared to 0.4% (1 of 260) in the control arms Diabetic macular edema and Diabetic Retinopathy In a pooled analysis of Studies D-1 and D-2, the ATE rate at 2 years was 7.2% (18 of 250) with 0.5 mg ranibizumab, 5.6% (14 of 250) with 0.3 mg ranibizumab, and 5.2% (13 of 250) with control. The stroke rate at 2 years was 3.2% (8 of 250) with 0.5 mg ranibizumab, 1.2% (3 of 250) with 0.3 mg ranibizumab, and 1.6% (4 of 250) with control. At 3 years, the ATE rate was 10.4% (26 of 249) with 0.5 mg ranibizumab and 10.8% (27 of 250) with 0.3 mg ranibizumab; the stroke rate was 4.8% (12 of 249) with 0.5 mg ranibizumab and 2.0% (5 of 250) with 0.3 mg ranibizumab Fatal events in patients with diabetic macular edema and diabetic retinopathy at baseline: A pooled analysis of Studies D-1 and D-2 showed that fatalities in the first 2 years occurred in 4.4% (11 of 250) of patients treated with 0.5 mg ranibizumab, in 2.8% (7 of 250) of patients treated with 0.3 mg ranibizumab, and in 1.2% (3 of 250) of control patients. Over 3 years, fatalities occurred in 6.4% (16 of 249) of patients treated with 0.5 mg ranibizumab and in 4.4% (11 of 250) of patients treated with 0.3 mg ranibizumab. Although the rate of fatal events was low and included causes of death typical of patients with advanced diabetic complications, a potential relationship between these events and intravitreal use of VEGF inhibitors cannot be excluded ADVERSE REACTIONS Serious adverse events related to the injection procedure have occurred in <0.1% of intravitreal injections, including endophthalmitis, rhegmatogenous retinal detachment, and iatrogenic traumatic cataract In ranibizumab-treated patients compared with the control group, the most common ocular side effects included conjunctival hemorrhage, eye pain, vitreous floaters, and intraocular pressure. The most common non-ocular side effects included nasopharyngitis, anemia, nausea, and cough As with all therapeutic proteins, there is the potential for an immune response in patients treated with ranibizumab products. The clinical significance of immunoreactivity to ranibizumab products is unclear at this time Postmarketing Experience The following adverse reaction has been identified during post-approval use of ranibizumab products: Ocular: Tear of retinal pigment epithelium among patients with neovascular AMD *An interchangeable product (IP) is a biological product that is approved based on data demonstrating that it is highly similar to an FDA-approved reference product (RP) and that there are no clinically meaningful differences between the products; it can be expected to produce the same clinical result as the RP in any given patient; and if administered more than once to a patient, the risk in terms of safety or diminished efficacy from alternating or switching between use of the RP and IP is not greater than that from the RP without such alternation or switch. Interchangeability of CIMERLI® has been demonstrated for the condition(s) of use, strength(s), dosage form(s), and route(s) of administration described in its Full Prescribing Information To report SUSPECTED ADVERSE REACTIONS, contact Coherus BioSciences at 1-800-483-3692 or FDA at 1-800-FDA-1088 or . For additional Safety Information, please see CIMERLI® Full Prescribing Information available here. About Coherus BioSciences Coherus is a commercial-stage biopharmaceutical company focused on the research, development and commercialization of innovative immunotherapies to treat cancer. Coherus’ strategy is to build a leading immuno-oncology franchise funded with cash generated through net sales of its diversified portfolio of FDA-approved therapeutics. In 2021, Coherus in-licensed toripalimab, an anti-PD-1 antibody, in the United States and Canada. The Biologics License Application for toripalimab in combination with chemotherapy as treatment for recurrent or metastatic nasopharyngeal carcinoma is currently under review by the FDA. Coherus markets UDENYCA® (pegfilgrastim-cbqv), a biosimilar of Neulasta®, CIMERLI® (ranibizumab-eqrn), a biosimilar of Lucentis®, and YUSIMRY™ (adalimumab-aqvh), a biosimilar of Humira®. Forward-Looking Statements Except for the historical information contained herein, the matters set forth in this press release are forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding Coherus’ ability to build its immuno-oncology franchise to achieve a leading market position; Coherus’ ability to generate cash and net sales; Coherus’ investment plans; Coherus’ ability to achieve approvals or launches of any of its product candidates; and expectations about maintaining or growing sales for any of Coherus’ products. Such forward-looking statements involve substantial risks and uncertainties that could cause Coherus’ actual results, performance or achievements to differ significantly from any future results, performance or achievements expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the risks and uncertainties inherent in the clinical drug development process; risks related to integration of Surface Oncology, Inc.’s programs and operations; risks related to Coherus’ existing and potential collaboration partners; risks of Coherus’ competitive position; the risks and uncertainties of the regulatory approval process, including the speed of regulatory review, international aspects of Coherus’ business and the timing of Coherus’ regulatory filings; the risk of FDA review issues; the risk that Coherus is unable to complete commercial transactions and other matters that could affect the availability or commercial potential of Coherus’ products and product candidates; and the risks and uncertainties of possible litigation. All forward-looking statements contained in this press release speak only as of the date of this press release. Coherus undertakes no obligation to update or revise any forward-looking statements. For a further description of the significant risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to Coherus’ business in general, see Coherus’ Quarterly Report on Form 10-Q for the fiscal quarter ended June 30, 2023 filed with the Securities and Exchange Commission on August 2, 2023, including the section therein captioned “Risk Factors” and in other documents Coherus files with the Securities and Exchange Commission. UDENYCA®, CIMERLI® and YUSIMRY™, whether or not appearing in large print or with the trademark symbol, are trademarks of Coherus, its affiliates, related companies or its licensors or joint venture partners unless otherwise noted. Trademarks and trade names of other companies appearing in this press release are, to the knowledge of Coherus, the property of their respective owners. Coherus Contact Information: For Investors & Media Jodi Sievers, VP, Corporate Communications ir@coherus.com

Drug ApprovalClinical ResultBiosimilar

13 Feb 2023

·www.biospace.com

Coherus Granted Permanent, Product-Specific Q-Code for CIMERLI® (ranibizumab-eqrn) from the Centers for Medicare and Medicaid Services

- Q-Code assigned to CIMERLI® for Medicare claims processing effective for dates of service on and after April 1, 2023 - - COHERUS Solutions™ patient services hub is available to facilitate successful access and reimbursement - REDWOOD CITY, Calif., Feb. 13, 2023 (GLOBE NEWSWIRE) -- Coherus BioSciences Inc. (“Coherus”, Nasdaq: CHRS) today announced that the Centers for Medicare and Medicaid Services (CMS) has published a new code pursuant to the Company’s application for Healthcare Common Procedure Coding System (HCPCS) Q-codes. The HCPCS Q-code assigned to CIMERLI® will be effective for patients administered CIMERLI® on or after April 1, 2023. Paul Reider, Chief Commercial Officer of Coherus, said, "This is an important milestone in the CIMERLI® launch. Beginning April 1st, use of CIMERLI’s permanent, product-specific Q-code will enable more efficient billing processes and speed time to reimbursement for providers. We believe that Q-code utilization will serve as a catalyst for market conversion, accelerating growth in 2023 starting in the second quarter. We want to thank CMS for its consideration and timely review of our Q-code application.” CIMERLI® is the first and only FDA-approved biosimilar interchangeable with Lucentis® (ranibizumab injection) for all indications including neovascular (wet) age-related macular degeneration (AMD), macular edema following retinal vein occlusion (RVO), diabetic macular edema (DME), diabetic retinopathy (DR), and myopic choroidal neovascularization (mCNV). CIMERLI® is contraindicated in patients with ocular or periocular infections or known hypersensitivity to ranibizumab products or any of the excipients in CIMERLI®. Hypersensitivity reactions may manifest as severe intraocular inflammation.1 Coherus Solutions™ offers healthcare professionals comprehensive practice and patient support that includes extensive patient assistance, industry-leading electronic services, and office support to ensure successful access and reimbursement. About Q-Codes Q-codes are permanent reimbursement codes granted to biosimilars and used by commercial insurance plans, Medicare, Medicare Advantage, and other government payers for Medicare Part B drugs like CIMERLI® that are administered by a physician. Claims submission and documentation are simplified with a permanent Q-code, facilitating and streamlining the billing and reimbursement process. About CIMERLI® CIMERLI® (ranibizumab-eqrn) is the first and only FDA-approved biosimilar interchangeable with Lucentis® for all Lucentis® FDA-approved indications. CIMERLI® has the same product attributes with Lucentis®, in terms of dosage strengths (0.3 mg, 0.5 mg), formulation and excipients, and amino acid sequence. CIMERLI® was approved by the FDA on August 2, 2022. Coherus owns the biologics license application (BLA) and commercial rights in the U.S. and its territories. Coherus licensed CIMERLI® from Bioeq AG, a joint venture between Polpharma Biologics Group B.V. and Formycon AG. 1. CIMERLI® (ranibizumab-eqrn) U.S. Prescribing Information, August 2022. IMPORTANT SAFETY INFORMATION & INDICATIONS CIMERLI® (ranibizumab-eqrn) is interchangeable* to Lucentis® (ranibizumab injection) CIMERLI® (ranibizumab-eqrn), a vascular endothelial growth factor (VEGF) inhibitor, is indicated for the treatment of patients with: Neovascular (Wet) Age-Related Macular Degeneration (AMD) Macular Edema Following Retinal Vein Occlusion (RVO) Diabetic Macular Edema (DME) Diabetic Retinopathy (DR) Myopic Choroidal Neovascularization (mCNV) CONTRAINDICATIONS CIMERLI® is contraindicated in patients with ocular or periocular infections or known hypersensitivity to ranibizumab products or any of the excipients in CIMERLI®. Hypersensitivity reactions may manifest as severe intraocular inflammation WARNINGS AND PRECAUTIONS Endophthalmitis and Retinal Detachments: Intravitreal injections, including those with ranibizumab products, have been associated with endophthalmitis and retinal detachments. Proper aseptic injection technique should always be utilized when administering CIMERLI®. Patients should be monitored following the injection to permit early treatment, should an infection occur Increases in Intraocular Pressure: Increases in intraocular pressure (IOP) have been noted both pre-injection and post-injection (at 60 minutes) with ranibizumab products. Monitor intraocular pressure prior to and following intravitreal injection with CIMERLI® and manage appropriately Thromboembolic Events: Although there was a low rate of arterial thromboembolic events (ATEs) observed in the ranibizumab clinical trials, there is a potential risk of ATEs following intravitreal use of VEGF inhibitors. ATEs are defined as nonfatal stroke, nonfatal myocardial infarction, or vascular death (including deaths of unknown cause) Neovascular (wet) age-related macular degeneration The ATE rate in the 3 controlled neovascular AMD studies during the first year was 1.9% (17 of 874) in the combined group of patients treated with 0.3 mg or 0.5 mg ranibizumab compared with 1.1% (5 of 441) in patients from the control arms. In the second year of Studies AMD-1 and AMD-2, the ATE rate was 2.6% (19 of 721) in the combined group of ranibizumab-treated patients compared with 2.9% (10 of 344) in patients from the control arms. In Study AMD-4, the ATE rates observed in the 0.5 mg arms during the first and second year were similar to rates observed in Studies AMD-1, AMD-2, and AMD-3 In a pooled analysis of 2-year controlled studies (AMD-1, AMD-2, and a study of ranibizumab used adjunctively with verteporfin photodynamic therapy), the stroke rate (including both ischemic and hemorrhagic stroke) was 2.7% (13 of 484) in patients treated with 0.5 mg ranibizumab compared to 1.1% (5 of 435) in patients in the control arms (odds ratio 2.2 [95% confidence interval (0.8-7.1)]) Macular edema following retinal vein occlusion The ATE rate in the 2 controlled RVO studies during the first 6 months was 0.8% in both the ranibizumab and control arms of the studies (4 of 525 in the combined group of patients treated with 0.3 mg or 0.5 mg ranibizumab and 2 of 260 in the control arms). The stroke rate was 0.2% (1 of 525) in the combined group of ranibizumab-treated patients compared to 0.4% (1 of 260) in the control arms Diabetic macular edema and Diabetic Retinopathy In a pooled analysis of Studies D-1 and D-2, the ATE rate at 2 years was 7.2% (18 of 250) with 0.5 mg ranibizumab, 5.6% (14 of 250) with 0.3 mg ranibizumab, and 5.2% (13 of 250) with control. The stroke rate at 2 years was 3.2% (8 of 250) with 0.5 mg ranibizumab, 1.2% (3 of 250) with 0.3 mg ranibizumab, and 1.6% (4 of 250) with control. At 3 years, the ATE rate was 10.4% (26 of 249) with 0.5 mg ranibizumab and 10.8% (27 of 250) with 0.3 mg ranibizumab; the stroke rate was 4.8% (12 of 249) with 0.5 mg ranibizumab and 2.0% (5 of 250) with 0.3 mg ranibizumab Fatal events in patients with diabetic macular edema and diabetic retinopathy at baseline: A pooled analysis of Studies D-1 and D-2 showed that fatalities in the first 2 years occurred in 4.4% (11 of 250) of patients treated with 0.5 mg ranibizumab, in 2.8% (7 of 250) of patients treated with 0.3 mg ranibizumab, and in 1.2% (3 of 250) of control patients. Over 3 years, fatalities occurred in 6.4% (16 of 249) of patients treated with 0.5 mg ranibizumab and in 4.4% (11 of 250) of patients treated with 0.3 mg ranibizumab. Although the rate of fatal events was low and included causes of death typical of patients with advanced diabetic complications, a potential relationship between these events and intravitreal use of VEGF inhibitors cannot be excluded ADVERSE REACTIONS Serious adverse events related to the injection procedure have occurred in <0.1% of intravitreal injections, including endophthalmitis, rhegmatogenous retinal detachment, and iatrogenic traumatic cataract In ranibizumab-treated patients compared with the control group, the most common ocular side effects included conjunctival hemorrhage, eye pain, vitreous floaters, and intraocular pressure. The most common non-ocular side effects included nasopharyngitis, anemia, nausea, and cough As with all therapeutic proteins, there is the potential for an immune response in patients treated with ranibizumab products. The clinical significance of immunoreactivity to ranibizumab products is unclear at this time Postmarketing Experience The following adverse reaction has been identified during post-approval use of ranibizumab products: Ocular: Tear of retinal pigment epithelium among patients with neovascular AMD *An interchangeable product (IP) is a biological product that is approved based on data demonstrating that it is highly similar to an FDA-approved reference product (RP) and that there are no clinically meaningful differences between the products; it can be expected to produce the same clinical result as the RP in any given patient; and if administered more than once to a patient, the risk in terms of safety or diminished efficacy from alternating or switching between use of the RP and IP is not greater than that from the RP without such alternation or switch. Interchangeability of CIMERLI® has been demonstrated for the condition(s) of use, strength(s), dosage form(s), and route(s) of administration described in its Full Prescribing Information. To report SUSPECTED ADVERSE REACTIONS, contact Coherus BioSciences, Inc. at 1-800-483-3692 or FDA at 1-800-FDA-1088 or . For additional Safety Information, please see CIMERLI® Full Prescribing Information available here. About Coherus BioSciences Coherus is a commercial-stage biopharmaceutical company focused on the research, development and commercialization of innovative immunotherapies to treat cancer. Coherus’ strategy is to build a leading immuno-oncology franchise funded with cash generated through net sales of its diversified portfolio of FDA-approved therapeutics. In 2021, Coherus in-licensed toripalimab, an anti-PD-1 antibody, in the United States and Canada. The BLA for toripalimab in combination with chemotherapy as treatment for recurrent or metastatic nasopharyngeal carcinoma is currently under review by the FDA. Coherus markets UDENYCA® (pegfilgrastim-cbqv), a biosimilar of Neulasta® (pegfilgrastim), and CIMERLI® (ranibizumab-eqrn), a biosimilar of Lucentis® (ranibizumab injection), in the U.S., and expects to launch the FDA-approved Humira® (adalimumab) biosimilar YUSIMRY™ (adalimumab-aqvh) in the U.S. in mid-2023. In January 2023, Coherus agreed to enter into definitive agreements providing for the acquisition of exclusive U.S. commercial rights to an Eylea® (aflibercept) biosimilar, FYB203, and plans to BLA for FYB203 in 2023. Forward-Looking Statements Except for the historical information contained herein, the matters set forth in this press release are forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding Coherus’ ability to build its immuno-oncology franchise to achieve a leading market position; Coherus’ ability to generate cash; Coherus’ investment plans; Coherus’ expectations for the launch date of YUSIMRY™; Coherus’ expectations about entering into definitive agreements and closing on those agreements to acquire exclusive U.S. commercial rights to an Eylea® biosimilar; expectations about Coherus’ ability to BLA for an Eylea® biosimilar; and expectations that obtaining a Q-code for CIMERLI® may result in market conversion or accelerating growth for CIMERLI® in the future;. Such forward-looking statements involve substantial risks and uncertainties that could cause Coherus’ actual results, performance or achievements to differ significantly from any future results, performance or achievements expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, risks and uncertainties of coordinating a launch for a new biosimilar in a competitive marketplace; risks and uncertainties inherent in the clinical drug development process; risks relating to executing business transactions; risks related to our existing and potential collaboration partners; risks of the drug development position of Coherus’ competitors; the risks and uncertainties of the regulatory approval process, including the speed of regulatory review, international aspects of Coherus’ business, the timing of Coherus’ regulatory filings; the risk of FDA review issues; the risk that Coherus is unable to complete commercial transactions and other matters that could affect the availability or commercial potential of Coherus’ drug candidates; and the risks and uncertainties of possible litigation. All forward-looking statements contained in this press release speak only as of the date of this press release. Coherus undertakes no obligation to update or revise any forward-looking statements. For a further description of the significant risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to Coherus’ business in general, see Coherus’ Annual Report on Form 10-Q for the quarter ended September 30, 2022, filed with the Securities and Exchange Commission on November 8, 2022, including the section therein captioned “Risk Factors” and in other documents that Coherus files with the Securities and Exchange Commission. UDENYCA®, CIMERLI®, COHERUS Solutions™ and YUSIMRY™, whether or not appearing in large print or with the trademark symbol, are trademarks of Coherus, its affiliates, related companies or its licensors or joint venture partners, unless otherwise noted. Trademarks and trade names of other companies appearing in this press release are, to the knowledge of Coherus, the property of their respective owners. Please see Prescribing Information for CIMERLI® (ranibizumab-eqrn). Coherus Contact Information: Investor Contact: Marek Ciszewski, SVP Investor Relations IR@coherus.com Media Contact: Jodi Sievers, VP Corporate Communications media@coherus.com

Drug ApprovalClinical ResultImmunotherapy

100 Deals associated with Verteporfin

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KEGG	Wiki	ATC	Drug Bank
D01162	Verteporfin	S01LA01	DB00460

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Histoplasmosis	US	Valeant Pharmaceuticals Luxembourg SARL	30 Jun 2008
Myopia	US	Valeant Pharmaceuticals Luxembourg SARL	30 Jun 2008
Age Related Macular Degeneration	JP	Clinigen KK	16 Oct 2003
Myopia, Degenerative	EU	CHEPLAPHARM Arzneimittel GmbH	27 Jul 2000
Myopia, Degenerative	IS	CHEPLAPHARM Arzneimittel GmbH	27 Jul 2000
Myopia, Degenerative	LI	CHEPLAPHARM Arzneimittel GmbH	27 Jul 2000
Myopia, Degenerative	NO	CHEPLAPHARM Arzneimittel GmbH	27 Jul 2000
Wet age-related macular degeneration	EU	CHEPLAPHARM Arzneimittel GmbH	27 Jul 2000
Wet age-related macular degeneration	IS	CHEPLAPHARM Arzneimittel GmbH	27 Jul 2000
Wet age-related macular degeneration	LI	CHEPLAPHARM Arzneimittel GmbH	27 Jul 2000
Wet age-related macular degeneration	NO	CHEPLAPHARM Arzneimittel GmbH	27 Jul 2000
Choroidal Neovascularization	US	Valeant Pharmaceuticals Luxembourg SARL	12 Apr 2000
Dystrophy, Macular	US	Valeant Pharmaceuticals Luxembourg SARL	12 Apr 2000

Developing

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Indication	Highest Phase	Country/Location	Organization	Date
Basal Cell Carcinoma, Multiple	Phase 3	-	QLT, Inc.	19 Nov 2002
Basal Cell Nevus Syndrome	Phase 3	-	QLT, Inc.	19 Nov 2002
Glycogen Storage Disease Type II	Phase 2	-	QLT, Inc.	01 Jan 2007

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03033225 (Pubmed \| Gastrointest Endosc)	Phase 2	Pancreatic Cancer	8	EUS-guided verteporfin PDT	rygcwbuozq(wnmmsbvsih) = bzjzhcctmw tkfjthrmqh (wwluijebmx ) View more	-	26 Feb 2021
AAO2020	Not Applicable	Uveal Melanoma	26	Primary PDT with Verteporfin	sfyhfhqncn(lwswxtgznh) = drpeicnsux jabmucxjoc (hsozmocgtj ) View more	-	13 Nov 2020
ASN2019	Not Applicable	Acute Kidney Injury YAP \| MCP1	-	Low-dose Verteporfin (LDVP) 25mg/kg	oqlyoceyxb(gejglwyifm) = tcuwrlbwng nrqpwaezqi (janufneslu )	Positive	05 Nov 2019
ASN2019	Not Applicable	Acute Kidney Injury YAP \| MCP1	-	High-dose Verteporfin (HDVP) 100mg/kg	oqlyoceyxb(gejglwyifm) = gwehutwkor nrqpwaezqi (janufneslu )	Positive	05 Nov 2019
NCT01846273 (EVEREST II, CTgov)	Phase 4	Age Related Macular Degeneration \| Polypoidal choroidal vasculopathy	321	Ranibizumab (Ranibizumab 0.5 mg + vPDT)	uoxihtihar(kfdqrgfrte) = jksjuzesvm xnxucuyxtb (ktustfpqiq, prrwwujhqj - mvdtktyuog) View more	-	07 Jun 2019
NCT01846273 (EVEREST II, CTgov)	Phase 4		321	Ranibizumab (Ranibizumab 0.5 mg)	uoxihtihar(kfdqrgfrte) = aoijisyvhd xnxucuyxtb (ktustfpqiq, gvqskxlzge - fgvscfizxx) View more	-	07 Jun 2019
NCT01846273 (Pubmed \| JAMA Ophthalmol) Manual	Phase 4	Polypoidal choroidal vasculopathy	322	verteporfin photodynamic therapy +Ranibizumab	mryzagccli(rzrifqaubz) = qvpehblqbd thoyxtqsks (iwzkkcsvkb ) View more	Positive	01 Nov 2017
NCT01846273 (Pubmed \| JAMA Ophthalmol) Manual	Phase 4	Polypoidal choroidal vasculopathy	322	Ranibizumab	mryzagccli(rzrifqaubz) = yolrlqekjc thoyxtqsks (iwzkkcsvkb ) View more	Positive	01 Nov 2017
ARVO2017	Not Applicable	Wet age-related macular degeneration	16	Adjunctive Indocyanine Green Angiography-Directed Verteporfin Photodynamic Therapy	gfkeblmndz(mlsxpuiysm) = naggylzyby iuulgmvatc (urpeyynnks )	-	01 Jun 2017
ARVO2014	Not Applicable	Polypoidal choroidal vasculopathy	27	Photodynamic therapy (PDT) combined with intravitreal injection of anti-VEGF	zjllldjkln(nqbtbduovz) = trniygugci gwijoqeoek (isjjpefwdb ) View more	-	01 Apr 2014
AAO2013	Not Applicable	Hemangioma	54	Photodynamic Therapy with Verteporfin	yazwwibyli(mdnmqdujec) = The BCVA improved by ≥ 2 Snellen lines in 50% and remained stable in 19% zryyyqrxml (gwfilixqom ) View more	-	17 Nov 2013
NCT01217944 (RADIANCE, CTgov)	Phase 3	Myopia, Degenerative \| Choroidal Neovascularization \| Vision, Low	277	Ranibizumab+Verteporfin PDT+Sham Ranibizumab	agatnjkywt(eeoolbpcmy) = fwpfgodvbw hjfstkxlhz (pkluirmyfr, qrsflljgne - pnckaovogo) View more	-	18 Oct 2013
NCT00527475 (CTgov)	Phase 2	Choroidal Neovascularization \| Age Related Macular Degeneration \| Glycogen Storage Disease Type II	60	ranibizumab (Group I)	kmgqruwrmi(njxbknjeti) = emqwgjyhsr ijarldehic (eyjtqudatd, uomblurako - ezvdvaxzsh) View more	-	07 Jun 2013
NCT00527475 (CTgov)	Phase 2		60	ranibizumab+verteporfin (Group II)	kmgqruwrmi(njxbknjeti) = qkxwtotjbf ijarldehic (eyjtqudatd, fupumbhina - pdrhidvndk) View more	-	07 Jun 2013

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