On May 15, 2025 Orna Therapeutics, a leading biotechnology company developing a proprietary pipeline of in vivo therapies across a broad range of autoimmune and oncology indications, reported the presentation of new preclinical data supporting its in vivo CAR therapy approach in autoimmune diseases during an oral session at the 28th American Society of Gene & Cell Therapy (ASGCT) (Free ASGCT Whitepaper) Annual Meeting being held May 13-17, 2025, in New Orleans, Louisiana (Press release, Orna Therapeutics, MAY 15, 2025, View Source [SID1234653178]).

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"The preclinical data presented today at ASGCT (Free ASGCT Whitepaper) highlight our potential to deliver on the promise of in vivo CAR T therapy," said Joseph Bolen, Ph.D., Chief Executive Officer of Orna Therapeutics. "Our CD19 panCAR program has demonstrated not only successful delivery of our lead panCAR LNP to disease-relevant immune cell types, but also robust and sustained B cell depletion at low doses in both peripheral blood and lymphoid tissues in non-human primates (NHPs). These compelling results continue to reinforce our commitment to translating our promising science into meaningful therapies for patients and we look forward to advancing our CD19 panCAR program towards the clinic in 2026."

Presentation Details:

Title: In Vivo panCAR Therapy Using Circular RNA for the Treatment of Autoimmune Disease

Speaker: Megan Hoban, Ph.D., panCAR Program Lead, Orna Therapeutics

Date/Time: Thursday, May 15, 2025, 8:00 AM – 9:45 AM CDT

Session Name: Cellular and Gene Therapies for Autoimmune Disease

Location: Room 388-390

In today’s presentation, Orna will showcase preclinical data demonstrating the potential of its in vivo panCAR therapy, enabled by its proprietary circular (oRNA) technology and best-in-class lipid nanoparticle (LNP) delivery system to achieve robust and sustained B cell depletion in both humanized mouse models and non-human primates across multiple doses.

Key findings from the study include:

Validated extra-hepatic delivery to disease-relevant immune cell types, including T cells, in mice and NHPs without requiring targeting ligands.
Lead panCAR LNP achieved over 60% delivery to peripheral blood and splenic T cells in NHPs.
CD19 panCAR doses as low as 0.03mpk led robust B cell depletion, with multi-dosing achieving increased B cell depletion in humanized mice.
In a humanized lupus mouse model, CD19 panCAR showed strong B cell depletion and a meaningful and differentiated reduction in dsDNA titers compared to rituximab.
CD19 panCAR induced full depletion of B cells across peripheral blood, spleen, lymph nodes, and bone marrow in NHPs, with peripheral B cells beginning to reconstitute after three weeks.

On May 15, 2025 City of Hope Research Spotlight offers a glimpse at groundbreaking scientific and clinical discoveries advancing lifesaving cures for patients with cancer, diabetes and other chronic, life-threatening diseases (Press release, City of Hope, MAY 15, 2025, View Source [SID1234653196]). Each spotlight features research-related news, such as recognitions, collaborations and the latest research defining the future of medical treatment.

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This roundup highlights diabetes research, the role of obesity in multiple myeloma, results from a clinical trial of a new liquid biopsy for evaluating potential responses to epidermal growth factor receptor (EGFR) inhibitors in metastatic colorectal cancers, the discovery of a biomarker that could predict a patient’s response to immune checkpoint inhibitors, a scientific statement from the American Heart Association on addressing cardiovascular toxicity in patients who had pediatric cancers and a study of a new medication that helps stop leukemia cells from decreasing the activity of the immune system.

To learn more about research at City of Hope, one of the largest and most advanced cancer research and treatment organizations in the United States, with its National Medical Center named top 5 in the nation for cancer by U.S. News & World Report, subscribe to City of Hope Research Spotlight.

HIRN Closes the Gap Between Vision and Victory in Type 1 Diabetes

A new report highlights the remarkable advances made in type 1 diabetes research since the National Institute of Diabetes and Digestive and Kidney Diseases established the Human Islet Research Network (HIRN) in 2014.

Lead author John Kaddis, City of Hope associate professor in the Department of Diabetes and Cancer Discovery Science within the Arthur Riggs Diabetes & Metabolism Research Institute, and members of the HIRN reflect on the past, present and future of type 1 diabetes research. The HIRN was formed to bring together experts from around the world to solve intractable problems in type 1 diabetes.

The article describes the milestones, achievements and critical goals of type 1 diabetes research, including:

Pioneering advances, technologies and systems that uncover the interactive role of insulin-producing beta cells within their physiological environment.
Innovative tools, disease models, devices and strategies that promote novel discoveries.
Shared resources, data access and interdisciplinary training to challenge scientific dogmas.
Although significant progress has been made, Kaddis emphasizes that successful approaches to preventing type 1 diabetes are still in their infancy. Kaddis and colleagues point out knowledge gaps in the processes underlying human beta cell loss, protection and replacement in type 1 diabetes.

Contributions by the HIRN are expanding scientific knowledge about the causes of type 1 diabetes and expediting the development of effective strategies to prevent, diagnose and treat the disease, the authors concluded.

For more information, see the journal article in Diabetes.

Exploring the role of obesity in progression from precursor condition to multiple myeloma

Patients with multiple myeloma incur some of the highest costs in cancer care to manage their disease. So, it’s imperative that people with a precursor condition called monoclonal gammopathy of undetermined significance (MGUS) know the risk factors that make progression to myeloma more likely.

To learn more about the role obesity plays in MGUS progression to cancer, a team led by Lawrence Liu, M.D., clinical fellow in hematology and medical oncology at City of Hope, and co-authors Murali Janakiram, M.D., M.S., of City of Hope and Su-Hsin Chang, Ph.D., of Washington University School of Medicine, which reviewed body mass index measurements over time in a cohort of nearly 22,500 people with MGUS.

The team’s findings, published recently in JAMA Network Open, suggest that maintaining a healthy weight may prevent MGUS from developing into myeloma. Using data collected about the patients by the U.S. Veterans Health Administration, the researchers tracked exposure to elevated body mass index for three years post-MGUS diagnosis.

Of the study participants, 21.7% had a healthy BMI between 18.5 to less than 25 at baseline. For this population, an increase of elevated BMI over time was associated with a higher risk of progression. Participants whose baseline BMI was 25 or greater had a 17% to 27% higher risk of progression to myeloma compared with patients with baseline BMI within the reference range. The researchers believe this cohort study is the first to quantify the association between cumulative exposure to BMI 25 or greater and the progression from MGUS to myeloma.

For more information, see the JAMA Network Open paper.

Predicting outcomes of EGFR inhibitors in metastatic colorectal cancer

In a recent paper published in Clinical Cancer Research, researchers from City of Hope, including corresponding author Ajay Goel, Ph.D., professor and chair of the Department of Molecular Diagnostics and Experimental Therapeutics, reported on outcomes from a clinical trial of a test to predict responses to certain medications in metastatic colorectal cancer (mCRC) patients.

The EXOsome and cell-free miRNAs of anti-EGFR ResistAnce (EXONERATE) interventional study developed, tested and validated a liquid biopsy to see how well it predicted progression-free survival, overall survival and objective response rate for two, first-line EGFR inhibitors — panitumumab or cetuximab — in mCRC.

Chemotherapy-naïve mCRC patients with certain genes (RAS wild-type) known to respond to EGRF inhibitors were recruited for two nationwide trials to receive cetuximab or panitumumab along with chemotherapy. The EXONERATE assay was developed using a technology called genome-wide small RNA sequencing to identify candidate biomarkers to predict good versus poor responders to the medications.

There can be different responses to treatment based on where the primary tumor is located in patients with mCRC — the disease is characterized as either right-sided or left-sided — so the researchers tested and validated the assay in both populations. They reported that the EXONERATE assay was successful at robustly predicting progression-free survival and overall survival outcomes in patients with mCRC, both right- and left-sided, before they received either panitumumab or cetuximab.

For more information, see the Clinical Cancer Research paper.

Searching for biomarkers to assess likely immune checkpoint inhibitor response

Immune checkpoint inhibitors, which block certain proteins that suppress the immune system so that their body can better fight cancer, have changed the landscape of cancer therapy in recent years. But because many patients do not see long-lasting benefits, better biomarkers are needed to assess likely response rates in patients.

Recently, a team of researchers led by Kelly Mahuron, M.D., an assistant clinical professor of surgical oncology at City of Hope, sought to pinpoint biomarkers for a positive response to a certain type of immune checkpoint inhibitors called PD-1 pathway inhibitors. Building on prior knowledge that CD8+ tumor infiltrating lymphocytes (TILs) have been associated with PD-1 inhibitor response, they aimed to identify the subpopulations that have the most prognostic value.

In a paper published in Cancer Research, Dr. Mahuron and other authors outlined a series of experiments to search for predictive biomarkers in 129 tumor samples from melanoma patients. Through studies that included single-cell analysis, the team found that advanced melanoma patients with more than or equal 20% of CD8+ TILs that co-expressed PD-1 proteins and CTLA-4 protein receptors (which they call CPHi TILs) had better objective response rates and survival following PD-1 monotherapy than those below this threshold. Based on these results, they believe the biomarker assay they developed can be used to predict an immune checkpoint inhibitor response.

The team utilized single cell RNA sequencing to further characterize CPHi TILs and they found that this cell population contains a diverse mix of subpopulations. Their findings have important implications for optimizing checkpoint-based immunotherapy across other cancers.

For more information, see the Cancer Research paper.

Addressing Heart Health in Pediatric Cancer Survivors

While pediatric patients represent just roughly 5% of new cancer cases each year, this population has high survival rates, making them vulnerable to therapy-related cardiovascular disease later in life. To highlight recent advances in the growing field of cardio-oncology, a group of committee members from the American Heart Association, including vice-chair Saro Armenian, D.O., M.P.H., the Barron Hilton Chair in Pediatrics and the director of the Childhood, Adolescent and Young Adult Survivorship Program, recently issued a scientific statement in the journal Circulation that offers updates on emerging concepts related to established cardiotoxic therapies.

The authors note that an increasing recognition that nearly all cancer treatments can pose risks for future cardiovascular disease has led to close investigations of anthracycline chemotherapy and chest-directed radiotherapy. As a result, dose reduction, use of cardioprotection for anthracyclines, and modern radiotherapy approaches have contributed to improved cardiovascular outcomes for survivors.

The statement includes considerations for newer treatments, such as small-molecule inhibitors and immunotherapies, that have expanded options for some patients but also revealed new cardiotoxic challenges. In addition, Dr. Armenian and the committee members focused on issues related to transition of care after cancer treatment, including surveillance and prevention strategies, examined the role physical activity should play in rehabilitation after pediatric cancer care, and provided updates on how to manage cardiovascular complications.

By incorporating new strategies in an equitable manner, the authors say adult cardiologists can help improve the transition from pediatric to adult care and greatly influence long-term health-related outcomes for childhood cancer survivors who are at risk for cardiovascular disease.

To read the entire statement, see the review paper in Circulation.

Keeping leukemia growth in check

For patients with chronic myeloid leukemia (CML), a goal of treatment is to keep the disease from progressing to a blast crisis (BC) or acute phase, in which the cancer becomes more aggressive. The mechanisms of transformation to the BC phase are not fully understood, but recent research led by Bin Zhang, Ph.D., associate professor in the Department of Hematologic Malignancies Translational Science, and Guido Marcucci, M.D., professor and chair of the Department of Hematologic Malignancies Translational Science, has revealed a new pathway that enables leukemia cells to decrease the ability of the immune system to fight CML growth.

A paper in Nature Communications unveils how an acquired deficit of a microRNA called miR-142 can cause the loss of T cells that play a crucial role in attacking cancer as CML progresses to the BC phase. In addition, the miR-142 mutation allows leukemic stem cells to evade the immune system and further promote disease growth.

However, the researchers also found that an miR-142 deficit can be promptly mitigated using a synthetic miR-142 mimic designed and synthesized at City of Hope called M-miR-142. Used alone or in combination with certain monoclonal antibodies and/or tyrosine kinase inhibitors, M-miR-142 extended survival in mouse models with BC CML.

According to the study, the experimental findings add important insights to the mechanisms of BC transformation and may offer conceptually new treatment strategies. A wide range of preclinical studies for M-miR-142 are underway, as the team hopes for a rapid translation of their findings from bench to bedside.

On May 15, 2025 Century Therapeutics, Inc. (‘Century’, NASDAQ: IPSC), an innovative biotechnology company developing induced pluripotent stem cell (iPSC)-derived cell therapies in autoimmune disease and cancer, reported financial results and business highlights for the first quarter ended March 31, 2025 (Press release, Century Therapeutics, MAY 15, 2025, View Source [SID1234653161]).

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"We have made important progress focusing on pipeline programs with transformational potential in high-value commercial markets. In a recently held company webinar and at ASGCT (Free ASGCT Whitepaper), we showcased developmental progress with our preclinical pipeline, iPSC platform, and manufacturing capabilities, highlighting the potential for a pathway to developing iPSC-derived cell therapies at antibody-like scale. We are on track to initiate IND-enabling studies for our lead preclinical program, CNTY-308, in mid-2025," said Brent Pfeiffenberger, Pharm.D., Chief Executive Officer of Century Therapeutics. "For our clinical-stage pipeline, patient dosing is now underway in the U.S. for the CALiPSO-1 trial and, with expansion into Europe, we remain on track to deliver clinical data for CNTY-101 by the end of 2025. We look forward to building on this momentum and pursuing a disciplined approach across our pipeline to bring investigational cell therapies closer to patients and generate value for all our stakeholders."

First Quarter 2025 and Recent Highlights

CNTY-101 in Autoimmune Disease

· Patient dosing underway in CALiPSO-1 trial in the U.S.: In March 2025, the first patient was dosed in the Phase 1 CALiPSO-1 trial which is currently evaluating CNTY-101 as a potential treatment for patients with B-cell-mediated autoimmune diseases.

· Focus on CALiPSO-1 clinical trial expansion and patient recruitment: Five clinical trial sites in the U.S. are active with additional U.S. clinical trial sites expected to open in 2025. Site activation activities are underway in select European countries, with enrollment at these sites expected to initiate in the second half of 2025. The company’s Clinical Trial Application (CTA) has been authorized in Germany, France, and Italy, providing important external validation of Century’s approach to clinical studies with allogeneic iPSC-derived therapies.

· CARAMEL IIT CTA authorized and study on track to commence in mid-2025: The CARAMEL investigator-initiated trial (IIT), a Phase 1/2 trial of CNTY-101 in patients with B-cell-mediated autoimmune diseases led by Professors Georg Schett and Andreas Mackensen and sponsored by the Friedrich-Alexander University Erlangen-Nürnberg, is expected to commence in mid-2025. The CTA has been authorized in Germany

· Clinical data by end of 2025: The company remains on track to report clinical data for CNTY-101 by the end of 2025.

CNTY-308 and Other Preclinical Programs

· ASGCT presentations highlighting preclinical pipeline: At the ongoing American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) 28th Annual Meeting, the company is presenting data on the company’s emerging preclinical cell therapy pipeline for autoimmune diseases and cancer. The data from the poster presentation suggest certain engineering modifications to CAR-iT and CAR-iNK cells can improve the anti-tumor activity of iPSC-derived immunotherapies to withstand the immunosuppressive nature of the solid tumor microenvironment. The data from the oral presentation characterize the generation of allogeneic iPSC-derived targeted CD4+/CD8+ ab CAR-T cells with comparable function, in vivo proliferation, and tumor control to primary T cells, supporting their use for the development of scalable, accessible CAR-T cell therapies.

· CNTY-308 on track to enter into IND-enabling studies in mid-2025: The company continues to expect to initiate Investigational New Drug (IND)-enabling studies with CNTY-308, a CD19-targeted CD4+/CD8+ ab CAR-iT cell therapy engineered with Allo-Evasion 5.0 as a potential treatment for B-cell-mediated autoimmune diseases and malignancies, in mid-2025.

· Progressing early-stage development activities for iPSC-derived ab CAR-T cells in oncology and opportunities with non-immune effector cells in high-impact diseases: The company is advancing CNTY-341, a CD19/CD22 dual-targeted CAR-iT investigational cell therapy intended for B-cell malignancies, and the company’s first solid tumor CAR-iT investigational program exploiting nectin-4 CAR and other validated targets. Each of these programs is anchored by advanced iPSC-derived ’tunable’ CD4+/CD8+ ab T cells and is engineered with the company’s proprietary immune evasion technology, Allo-Evasion 5.0, which is designed to enable holistic evasion of T cell, NK cell, and humoral immunity. In addition, the company is leveraging its deep expertise in selective iPSC differentiation to non-immune effector cells with opportunities to potentially accelerate in high-impact therapeutic areas where the company believes its technology and capabilities provide meaningful differentiation.

First Quarter 2025 Financial Results

· Cash Position: Cash, cash equivalents, and marketable securities were $185.8 million as of March 31, 2025, as compared to $220.1 million as of December 31, 2024. The company estimates its cash, cash equivalents, and investments will support operations into the fourth quarter of 2026.

· Collaboration Revenue: Collaboration revenue generated through the company’s collaboration, option, and license agreement with Bristol-Myers Squibb (the Collaboration Agreement) was $109.2 million for the three months ended March 31, 2025, compared to $0.9 million for the same period in 2024. The Collaboration Agreement was terminated effective March 12, 2025. As such, the company recognized $109.2 million of collaboration revenue for the quarter ended March 31, 2025. There will be no future collaboration revenues recognized under the Collaboration Agreement.

· Research and Development (R&D) Expenses: R&D expenses were $26.6 million for the three months ended March 31, 2025, compared to $23.4 million for the same period in 2024. The increase in R&D expenses is most notably due to increased clinical trial costs and advancing of preclinical programs.

· General and Administrative (G&A) Expenses: G&A expenses were $8.4 million for the three months ended March 31, 2025, compared to $8.7 million for the same period in 2024. The decrease was primarily due to a decrease in salary and benefit expense.

· Net Income (Loss): Net income was $76.6 million for the three months ended March 31, 2025, compared to net (loss) of $28.1 million for the same period in 2024.

On May 15, 2025 Phio Pharmaceuticals Corp. (Nasdaq: PHIO) is a clinical-stage biopharmaceutical company developing therapeutics that use its INTASYL siRNA gene silencing technology designed to make the body’s immune cells more effective in killing cancer cells, reported its financial results for the quarter ended March 31, 2025 and provided a business update (Press release, Phio Pharmaceuticals, MAY 15, 2025, View Source [SID1234653179]).

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Recent Corporate Updates

PH-762 Clinical Progress

Phio’s ongoing Phase 1b dose escalation clinical trial (NCT 06014086) is designed to evaluate the safety and tolerability of neoadjuvant use of intratumoral PH-762 in Stages 1, 2 and 4 cutaneous squamous cell carcinoma (cSCC), Stage 4 melanoma, and Stage 4 Merkel cell carcinoma.

To date, a total of 10 patients with cutaneous carcinomas have been treated in Cohorts 1, 2 and 3. These cohorts included 9 patients with cSCC and 1 patient with metastatic melanoma. At Day 36 (planned tumor excision), of the 9 patients with cSCC, 4 patients had a pathologic complete response (100% tumor clearance). One patient had a near complete response (>90% clearance) and 1 patient had a partial response (>50% clearance). The other 3 cSCC and one metastatic melanoma patient had a pathologic non-response (< 50% clearance). Patients with a pathologic complete response (100% tumor clearance) may have visual signs of residual scar or subdermal inflammation prior to resection. No patients, however, exhibited clinical progression of disease.

To date, there were no dose-limiting toxicities or clinically relevant treatment-emergent adverse effects in the patients receiving intratumoral PH-762 in this trial. Moreover, PH-762 has been well tolerated in all enrolled patients in each escalating dose cohort.

The fourth cohort is currently enrolling and treating patients; Phio expects to complete enrollment in the trial in the third quarter of 2025.

Scientific News

During the three months ended March 31, 2025, Phio was awarded podium presentations for its INTASYL self-delivering siRNA technology at the American Academy of Dermatology (AAD) and at the Society of Investigative Dermatology (SID). The Company presented its phase 1b clinical trial results to date. The Company also presented data on INTASYL compounds PH-762 and PH-894 at the 11th Annual Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) (ITOC 11) conference in Munich, Germany.

The Company’s INTASYL compound RXI-231 was highlighted in the peer reviewed journal, Clinical, Cosmetic and Investigational Dermatology. The article presented proof-of-concept data for RXI-231, an INTASYL compound designed to target and reduce tyrosinase (TYR) gene expression. While further characterization and clinical testing is needed, RXI-231 shows promise in treating hyperpigmentation disorders.

Capital Sourcing

In December 2024 and January 2025, Phio raised an aggregate of approximately $9.2 million in registered direct offerings and concurrent private placements, before deduction of commissions and other expenses. Additional gross proceeds of approximately $2.9 million were raised from the exercise of warrants previously issued on July 12, 2024. With these proceeds, the Company now believes it has sufficient capital to complete the treatment phase of the Phase 1b trial.

Cost Rationalization

From April 2014 to March 2024, the Company leased space that was utilized as its corporate headquarters and primary laboratory. The lease expired on March 31, 2024. On March 1, 2024, the Company commenced a lease for a laboratory facility located at 17 Briden Street, Worcester, Massachusetts. The lease had an original expiration date of August 31, 2024, and was subsequently extended through February 28, 2025. The Company continues to lease the space on a month-to-month basis. Monthly rent is approximately $2,500. In March 2025, the Company contracted with LifeSciences PA located at 411 Swedeland Road, King of Prussia, PA 19406 for access to full working space for normal hours of operations at a fee of $300 per month, which can be cancelled at any time.

In May 2024, the Company terminated the Clinical Co-Development Agreement with AgonOx, Inc. (AgonOx) effective immediately. The Company paid AgonOx all payment obligations that accrued prior to the termination of the Clinical Co-Development Agreement. The Company made the remaining payment of $34,320, which primarily related to accrued obligations for patient fees and other miscellaneous costs as of the date of termination to AgonOx on March 21, 2025. This settled all future obligations to AgonOx.

Financial Results

Cash Position

At March 31, 2025, the Company had cash of approximately $13.3 million as compared with approximately $5.4 million at December 31, 2024.

Net cash provided by financing activities for the three months ended March 31, 2025 was approximately $9.2 million as compared to the three months ended March 31, 2024 where net cash used in financing activities was approximately $4,000. The increase in net cash provided by financing activities was primarily due to the issuance of common stock and warrants, and the exercise of warrants.

Research and Development Expenses

Research and development expenses were $0.886 million for the three months ended March 31, 2025 as compared with $1.148 million for the three months ended March 31, 2024, a decrease of 23%. The decrease in research and development expenses was primarily driven by decreases in salary-related costs and in consulting expense.

General and Administrative Expenses

General and administrative expenses were approximately $0.986 million for the three month period ended March 31, 2025 as compared with approximately $1.061 million for the three months ended March 31, 2024, a decrease of 7%. The Company considers this to be an immaterial fluctuation.

Net Loss

Net loss was $1.8 million for the three months ended March 31, 2025 as compared with $2.2 million for the three months ended March 31, 2024. The decrease in net loss was due to the reductions in research and development and general and administrative expenses cited above.

On May 15, 2025 Incyte (Nasdaq:INCY) reported that the U.S. Food and Drug Administration (FDA) has approved Zynyz (retifanlimab-dlwr), a humanized monoclonal antibody targeting programmed death receptor-1 (PD-1), in combination with carboplatin and paclitaxel (platinum-based chemotherapy) for the first-line treatment of adult patients with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC) (Press release, Incyte, MAY 15, 2025, View Source [SID1234653197]). In addition, the FDA granted approval for Zynyz as a single agent for the treatment of adult patients with locally recurrent or with metastatic SCAC with disease progression on or intolerance to platinum-based chemotherapy.

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"The FDA approval of Zynyz marks a pivotal moment, bringing effective combination and monotherapy treatment options to patients with advanced anal cancer after decades of limited innovation," said Hervé Hoppenot, Chief Executive Officer, Incyte. "At Incyte, we focus our efforts where we can make the biggest impact for patients. I am proud of our scientists and development teams for their perseverance in delivering the first approved PD-1 inhibitor to U.S. patients with SCAC."

The Priority Review and FDA approval of the supplemental Biologics License Application (sBLA) for Zynyz was based on data from two trials: the Phase 3 POD1UM-303/InterAACT2 trial evaluating Zynyz in combination with platinum-based chemotherapy (carboplatin-paclitaxel) in adult patients with metastatic or inoperable locally recurrent SCAC not previously treated with systemic chemotherapy, and the Phase 2 POD1UM-202 trial evaluating Zynyz monotherapy in previously treated patients with locally advanced or metastatic SCAC who have progressed on or were intolerant of platinum-based chemotherapy.

Results from POD1UM-303/InterAACT2, featured at a Presidential Symposium on Practice-Changing Trials at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) in 2024, showed a clinically meaningful and statistically significant 37% reduction in the risk of progression or death (P=0.0006). Patients in the Zynyz and chemotherapy combination group achieved a median progression-free survival (PFS) of 9.3 months compared to 7.4 months for patients in the placebo combination group. Additionally, a 6.2-month improvement in median overall survival (OS) was observed (P=0.0273) at an interim analysis; OS follow-up is ongoing. No new safety signals were observed. Serious adverse reactions occurred in 47% of patients receiving Zynyz in combination with chemotherapy. The most frequent serious adverse reactions (≥ 2% of patients) were sepsis (3.2%), pulmonary embolism (3.2%), diarrhea (2.6%) and vomiting (2.6%).

"Patients with inoperable locally recurrent or metastatic anal cancer have historically faced poor five-year survival rates and limited treatment options.1 The POD1UM data highlight the potential of Zynyz to be a meaningful new option, and notably demonstrate that the addition of Zynyz to platinum-based chemotherapy significantly improves progression-free survival," said Marwan Fakih, M.D., Professor, Medical Oncology & Therapeutics Research, Associate Director, Clinical Sciences, Medical Director, Briskin Center for Clinical Research, Division Chief, GI Medical Oncology, Co-Director, Gastrointestinal Cancer Program, City of Hope. "This approval marks an important advancement as it makes a new treatment approach available for this challenging cancer."

The Zynyz monotherapy approval is based on results from the POD1UM-202 study which demonstrated that treatment with Zynyz monotherapy produced an objective response rate (ORR) of 14% and disease control rate of 49%. Zynyz demonstrated a safety profile as expected of a PD-1 inhibitor with no loss of human immunodeficiency virus (HIV) infection control.2 Serious adverse reactions occurred in 40% of patients receiving Zynyz. The most frequent serious adverse reactions (≥ 2% of patients) were non-urinary tract infection, perineal pain, abdominal pain, anemia, hemorrhage, diarrhea, pyrexia, urinary tract infection, musculoskeletal pain and dyspnea.

"Patients with anal cancer often face a troubling lack of public awareness and understanding when it comes to risk factors, symptoms and their overall cancer journey," said David Winterflood, Chief Executive Officer of the Anal Cancer Foundation. "The approval of Zynyz marks a step forward for advanced SCAC treatment, brings attention to a long-overlooked condition with limited treatment options and offers patients whose anal cancer has returned or spread an option to treat their disease."

In addition to the sBLA in the U.S., Incyte submitted a Type II variation Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for retifanlimab in advanced SCAC and a Japanese New Drug Application (J-NDA) which was accepted by the Pharmaceuticals and Medical Devices Agency (PMDA) for retifanlimab in advanced SCAC.

Incyte is committed to supporting patients and removing barriers to access medicines. Eligible patients in the U.S. who are prescribed Zynyz have access to IncyteCARES (Connecting to Access, Reimbursement, Education and Support), a comprehensive program offering personalized patient support, including financial assistance and ongoing education and additional resources. More information about IncyteCARES is available by visiting www.incytecares.com or calling 1-855-452-5234, Monday through Friday, from 8 a.m. to 8 p.m. ET.

About Squamous Cell Carcinoma of the Anal Canal (SCAC)

SCAC is the most common type of anal cancer, making up 85% of cases.3 It is a rare disease for which the incidence is increasing approximately 3% per year.4 About 90% of cases are associated with human papillomavirus (HPV) infection—the number one risk factor for anal cancer.5 HIV is an important amplifier of anal cancer, as people with HIV are 25 to 35 times more likely to develop it.6,7 Anal cancer shares many of the same symptoms as non-cancerous conditions, such as hemorrhoids—including pain, itching, a lump or mass and changes in bowel movements—and as a result can go undetected leading to the majority of patients presenting with locally advanced disease.2,8 More information about SCAC is available by visiting www.analcancer.com.

About POD1UM

The POD1UM (PD1 Clinical Program in Multiple Malignancies) clinical trial program for retifanlimab includes POD1UM-303, POD1UM-202 and several other Phase 1, 2 and 3 studies for patients with solid tumors, including a registration-directed trial evaluating retifanlimab in combination with platinum-based chemotherapy for patients with non-small cell lung cancer.

About Zynyz (retifanlimab-dlwr)

Zynyz (retifanlimab-dlwr) is a humanized monoclonal antibody targeting programmed death receptor-1 (PD-1), indicated in combination with carboplatin and paclitaxel (platinum-based chemotherapy) for the first-line treatment of adult patients with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC) and as a single agent for the treatment of adult patients with locally recurrent or metastatic SCAC with disease progression or intolerance to platinum-based chemotherapy in the U.S.

Zynyz is also indicated for the treatment of adult patients with metastatic or recurrent locally advanced Merkel cell carcinoma (MCC) in the U.S. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Zynyz is marketed by Incyte in the United States. In 2017, Incyte entered into an exclusive collaboration and license agreement with MacroGenics, Inc. for global rights to retifanlimab.

Zynyz is a registered trademark of Incyte.

Important Safety Information

What is the most important information I should know about Zynyz?

Zynyz is a medicine that may treat certain types of cancers by working with your immune system. Zynyz can cause your immune system to attack normal organs and tissues in any area of your body and can affect the way they work. These problems can sometimes become severe or life-threatening and can lead to death. You can have more than one of these problems at the same time. These problems may happen anytime during treatment or even after your treatment has ended.

Call or see your doctor right away if you develop any new or worsening signs or symptoms, including:

Lung problems: cough, shortness of breath, chest pain

Intestinal problems: diarrhea (loose stools) or more frequent bowel movements than usual; stools that are black, tarry, sticky, or have blood or mucus; severe stomach-area (abdomen) pain or tenderness

Liver problems: yellowing of your skin or the whites of your eyes; severe nausea or vomiting; pain on the right side of your stomach area (abdomen); dark urine (tea colored); bleeding or bruising more easily than normal

Hormone gland problems: headaches that will not go away or unusual headaches; eye sensitivity to light; eye problems; rapid heartbeat; increased sweating; extreme tiredness; weight gain or weight loss; feeling more hungry or thirsty than usual; urinating more often than usual; hair loss; feeling cold; constipation; your voice gets deeper; dizziness or fainting; changes in mood or behavior, such as decreased sex drive, irritability, or forgetfulness

Kidney problems: decrease in your amount of urine, blood in your urine, swelling of your ankles, loss of appetite

Skin problems: rash; itching; skin blistering or peeling; painful sores or ulcers in your mouth or nose, throat, or genital area; fever or flu-like symptoms; swollen lymph nodes

Problems can also happen in other organs and tissues. These are not all of the signs and symptoms of immune system problems that can happen with Zynyz. Call or see your doctor right away for any new or worsening signs or symptoms, which may include:

chest pain, irregular heartbeat, shortness of breath, or swelling of ankles
confusion, sleepiness, memory problems, changes in mood or behavior, stiff neck, balance problems, tingling or numbness of the arms or legs
double vision, blurry vision, sensitivity to light, eye pain, changes in eyesight
persistent or severe muscle pain or weakness, muscle cramps
low red blood cells, bruising
Infusion reactions that can sometimes be severe. Signs and symptoms of infusion reactions may include: chills or shaking, itching or rash, flushing, shortness of breath or wheezing, dizziness, feel like passing out, fever, back or neck pain.

Rejection of a transplanted organ or tissue. Your doctor should tell you what signs and symptoms you should report and monitor you, depending on the type of organ or tissue transplant that you have had.

Complications, including graft-versus-host disease, in people who have received a bone marrow (stem cell) transplant that uses donor stem cells (allogeneic). These complications can be serious and can lead to death. These complications may happen if you underwent transplantation either before or after being treated with Zynyz. Your doctor will monitor you for these complications.

Getting medical treatment right away may help keep these problems from becoming more serious. Your doctor will check you for these problems during your treatment. Your doctor may treat you with corticosteroid or hormone replacement medicines and may also need to delay or completely stop treatment if you have severe side effects.

Before you receive Zynyz, tell your doctor about all of your medical conditions, including if you:

have immune system problems such as Crohn’s disease, ulcerative colitis, or lupus
have received an organ transplant or tissue transplant, including corneal transplant
have received or plan to receive a stem cell transplant that uses donor stem cells (allogeneic)
have received radiation treatment to your chest area
have a condition that affects your nervous system, such as myasthenia gravis or Guillain-Barré syndrome
are pregnant or plan to become pregnant. Zynyz can harm your unborn baby
Females who are able to become pregnant:

Your doctor should do a pregnancy test before you start treatment.
You should use an effective method of birth control during your treatment and for 4 months after your last dose. Talk to your doctor about birth control methods that you can use during this time.
Tell your doctor right away if you become pregnant or think you may be pregnant during treatment.
are breastfeeding or plan to breastfeed. It is not known if Zynyz passes into your breast milk. Do not breastfeed during treatment and for 4 months after your last dose
Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

The most common side effects of Zynyz when given with the chemotherapy medicines carboplatin and paclitaxel in people with SCAC include tiredness, numbness, pain, tingling, or burning in your hands or feet; nausea; hair loss; diarrhea; muscle and bone pain; constipation; bleeding; rash; vomiting; decreased appetite; itching; stomach-area pain.

The most common side effects of Zynyz when used alone in people with SCAC include tiredness, muscle and bone pain, diarrhea, infection, rectal or genital-area pain, bleeding, urinary tract infection (UTI), rash, nausea, loss of appetite, constipation, stomach-area pain, shortness of breath, fever, vomiting, cough, itching, low levels of thyroid hormone, headache, decreased weight.

The most common side effects of Zynyz when used alone in people with MCC include tiredness, muscle and bone pain, itching, diarrhea, rash, fever, nausea.

These are not all the possible side effects of Zynyz. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may also report side effects to Incyte Corporation at 1-855-463-3463.

General information about the safe and effective use of Zynyz

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. If you would like more information about Zynyz, talk with your doctor. You can ask your doctor for information about Zynyz that is written for health professionals.

Please see the full Prescribing Information, including the Medication Guide, for Zynyz.

You may also report side effects to the FDA View Source or to Incyte Corporation at 1-855-463-3463.