Acral Lentiginous Malignant Melanoma

SAN FRANCISCO and SUZHOU, China, Sept. 3, 2024 /PRNewswire/ -- Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, cardiovascular and metabolic, autoimmune, ophthalmology and other major diseases, announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track Designation to its PD-1/IL-2α Bispecific Antibody Fusion Protein (R&D code: IBI363) for the treatment of unresectable locally advanced or metastatic melanoma (except choroidal melanoma) in patients who have progressed after at least one line of systemic therapy, which must include a PD-1/L1 inhibitor. Phase 1/2 clinical trials are currently underway in China, the U.S., and Australia to assess IBI363's efficacy and safety in various advanced malignant tumors. At the ESMO Plenary meeting on June 14, 2024, Innovent presented promising efficacy signals in melanoma patients who had previously undergone immunotherapy: 37 patients with melanoma who had previously received immunotherapy received 1mg/kg of IBI363 and underwent at least one tumor evaluation after baseline, and 11 patients achieved objective responses, including 1 CR and 10 PR, with ORR and DCR of 29.7% and 73.0%, respectively. (Link) Dr. Hui Zhou, Senior Vice President of Innovent, said, "Melanoma is the most common fatal skin cancer in Europe and the United States. In China, while melanoma is a rare malignant tumor, it has a high fatality rate, and its incidence is steadily increasing each year. Despite the success of immune checkpoint inhibitors in the treatment of melanoma, there is currently no drug approved for immunotherapy failed melanoma around the world, and the ORR of traditional chemotherapy ± anti-vascular therapy for immunotherapy failed melanoma is only 3.8% to 6.8%, with a median PFS of less than 3 months, and the benefit is very limited[1]-[2]. Therefore, there is an urgent clinical need for patients who have previously failed immunotherapy. As a First in-class PD-1/IL-2α-bias bispecific antibody fusion protein, IBI363 monotherapy has shown encouraging efficacy and a favorable safety profile in melanoma subjects who have previously received immunotherapy. We will continue to explore the efficacy and safety of IBI363 in melanoma to provide more effective clinical treatment for patients with immune-resistant melanoma." Fast Track Designation (FTD) is a rapid review process designed to facilitate the clinical development of a drug that may treat serious conditions and fulfill an unmet medical need. According to regulations, drug candidates that obtain FTD qualifications will have more opportunities to communicate with the FDA during subsequent drug development and review processes, which will help speed up the clinical development and approval of the drug. About Melanoma Melanoma is a malignant tumor that develops from melanocytes and is the fifth most common cause of cancer in the United States[3]. Although melanoma represents only 3% of all skin cancer cases, it has the highest mortality rate and is the most prone to metastasize. In China, both the incidence and mortality rates of melanoma have been steadily rising over the years. According to the classification of the disease site, melanoma is mainly divided into skin melanoma, acral and mucosal melanoma. Chinese melanoma differs greatly from European and American Caucasian melanoma in pathogenesis, biological behavior, histological morphology, treatment and prognosis[4]. For advanced cutaneous and acral melanomas, for those carrying BRAF V600 mutation, BRAF inhibitor combined with MEK inhibitor is the preferred molecular targeted therapy. For patients without a BRAF V600 mutation, comination of chemotherapy and anti-angiogenic drugs may be considered as the first-line treatment. Immunotherapy has not been approved as the first-line treatment indication for advanced melanoma in China. For second-line treatment, therapies not used in the first-line are recommended. If a PD-1 monoclonal antibody was not administered initially, it can be selected for the second-line. In advanced mucosal melanoma, chemotherapy or a combination of PD-1 monoclonal antibody and anti-angiogenic drugs may be considered as first-line options. For patients with BRAF V600 mutation, a BRAF inhibitor ±MEK inhibitor can be chosen. Currently, posterior treatment options for melanoma are very limited[5]. About IBI363 (PD-1/IL-2 α ) IBI363 is a first-in-class drug candidate independently developed by Innovent Biologics. Its active ingredient is PD-1/IL-2 bispecific antibody fusion protein. The IL-2 arm of IBI363 has been engineered to maximize efficacy and reduce toxicity, whereas the PD-1 binding arm achieves PD-1 blockade and selective IL-2 delivery. Therefore, IBI363 functions by simultaneously blocking the PD-1/PD-L1 pathway and activating the IL-2 pathway, enabling more precise and efficient targeting and activation of tumor specific T cells. IBI363 has demonstrated notable anti-tumor activity across various tumor-bearing pharmacological models and showed significant antitumor efficacy in both PD-1 resistant and metastatic models. Additionally, IBI363 exhibited a favorable safety profile in preclinical models. Clinical studies of IBI363 are currently underway in China, the United States, and Australia to evaluate its safety, tolerability and preliminary efficacy in subjects with advanced malignancies. About Innovent Innovent is a leading biopharmaceutical company founded in 2011 with the mission to empower patients worldwide with affordable, high-quality biopharmaceuticals. The company discovers, develops, manufactures and commercializes innovative medicines that treat some of the most intractable diseases. Its pioneering therapies treat cancer, cardiovascular and metabolic, autoimmune and eye diseases. Innovent has 11 products in the market, 3 new drug applications under the NMPA review, 4 assets in Phase III or pivotal clinical trials and 18 more molecules in early clinical stage. Innovent partners with over 30 global healthcare leaders, including Eli Lilly, Roche, Sanofi, Adimab, Incyte and MD Anderson Cancer Center. Guided by the motto, "Start with Integrity, Succeed through Action," Innovent maintains the highest standard of industry practices and works collaboratively to advance the biopharmaceutical industry so that first-rate pharmaceutical drugs can become widely accessible. For more information, visit , or follow Innovent on Facebook and LinkedIn. Statement: Innovent does not recommend the use of any unapproved drug (s)/indication (s). Forward-Looking Statements This news release may contain certain forward-looking statements that are, by their nature, subject to significant risks and uncertainties. The words "anticipate", "believe", "estimate", "expect", "intend" and similar expressions, as they relate to Innovent, are intended to identify certain of such forward-looking statements. Innovent does not intend to update these forward-looking statements regularly. These forward-looking statements are based on the existing beliefs, assumptions, expectations, estimates, projections and understandings of the management of Innovent with respect to future events at the time these statements are made. These statements are not a guarantee of future developments and are subject to risks, uncertainties and other factors, some of which are beyond Innovent's control and are difficult to predict. Consequently, actual results may differ materially from information contained in the forward-looking statements as a result of future changes or developments in our business, Innovent's competitive environment and political, economic, legal and social conditions. Innovent, the Directors and the employees of Innovent assume (a) no obligation to correct or update the forward-looking statements contained in this site; and (b) no liability in the event that any of the forward-looking statements does not materialize or turn out to be incorrect. SOURCE Innovent Biologics

MDNA11 continues to demonstrate encouraging single-agent activity from the dose escalation and evaluation portion of the ABILITY-1 Study including deep ongoing partial responses with 100% reduction of target lesions in one pancreatic and 70% reduction of target lesion in one melanoma cancer patientMDNA11 also showed durable stable disease in 3 melanoma patients for at least 5 months to 18 months with concomitant shrinkage of tumor size following failure with check-point inhibitor therapiesMDNA11 is generally well tolerated with no dose-limiting toxicities or vascular leak syndrome reported in any of the dose escalation cohortsMedicenna believes that these data reaffirm the differentiated and promising therapeutic activity, safety, PD and PK profile of the ‘beta-enhanced not-alpha’ albumin-fused IL-2 superkine in patients with advanced solid tumors who have failed current standard of care TORONTO and HOUSTON, Nov. 06, 2023 (GLOBE NEWSWIRE) -- Medicenna Therapeutics Corp. (“Medicenna” or the “Company”) (TSX: MDNA), a clinical-stage immunotherapy company focused on the development of Superkines, today announced that new clinical data from the Phase 1 monotherapy dose escalation/evaluation portion of the Phase 1/2 ABILITY-1 (A Beta-only IL-2 ImmunoTherapY) study evaluating MDNA11, the only long-acting, ‘beta-enhanced not-alpha’ interleukin-2 (IL-2) super-agonist in clinical development, in patients with advanced solid tumors, were presented at the 38th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) held in San Diego, CA, on November 4th, 2023. “We are very encouraged by two partial responses and three durable stable diseases in patients with advanced cancer who had progressed on multiple prior therapies, reinforcing MDNA11’s promising single-agent activity,” said Fahar Merchant, Ph.D., President and Chief Executive Officer of Medicenna. “These data add to the growing body of evidence demonstrating the clinical effectiveness of MDNA11 with highly favorable underlying immune response characterized by robust expansion and activation of CD8+ T cells with minimal impact on immune-suppressive Tregs. MDNA11 with uniquely differentiating ‘beta-enhanced not-alpha’ features, continues to be a potential best-in-class next-generation IL-2 super-agonist for treatment of advanced solid tumors. We look forward to reporting results from the monotherapy expansion and combination escalation arms of the Phase 2 study in the first half of 2024.” Key findings from the Phase 1 monotherapy dose escalation portion of the ABILITY-1 study at time of data cut-off (26-Oct-2023) include: Favorable safety profile: No dose limiting toxicity (DLT) reported and no evidence of vascular leak syndrome (VLS). Vast majority (95.6%) of treatment-related adverse events (TRAEs) were of grade 1-2 severity and resolved within 48 hours; grade 3 TRAEs mainly constituted transient LFT elevations; no grade 4 or 5 events were reported. Encouraging single-agent anti-tumor activity at doses of 60 ug/kg (N = 15): Partial response reported in 2 patients with aggressive tumor types A patient with metastatic pancreatic ductal adenocarcinoma (PDAC; MSI-H), who had previously failed on multiple systemic therapies and exhibited primary resistance to immune checkpoint inhibitors, experienced remarkable response to MDNA11 (60 ug/kg) with baseline target lesions and non-target lesions showing deepening shrinkage on successive imaging scans. Following return from a 7 week vacation, a single new lesion was observed and MDNA11 treatment was resumed. Prior to receiving one cycle of radiotherapy for the new lesion, complete resolution of initial 2 target and 1 non-target lesions was achieved. Patient continues on MDNA11 post radiotherapy.A patient with cutaneous melanoma, who progressed on prior line of dual checkpoint inhibitors, treated with MDNA11 (90 ug/kg dose), showed a 70% reduction of the target lymph node lesion at week 12. Durable stable disease in 3 metastatic melanoma patients with concomitant reduction in tumor burden: Two patients with SD of >20 (acral melanoma) and >24 weeks (cutaneous melanoma) are continuing MDNA11 treatment in the 120 ug/kg cohort. One patient with cutaneous melanoma had SD for > 1.5 years having started MDNA11 at the 10 ug/kg dose with subsequent intra-patient dose escalations of 30, 60 and 90 ug/kg. Potent proliferation of effector immune populations: Pharmacodynamic data showed robust and durable activation of effector immune cells, particularly CD8+ T cells (CD25+, OX40+), with minimal impact on the immunosuppressive Treg population. Recommended Dose for Expansion (RDE): Target dose of 90 ug/kg (following two step-up doses of 30 and 60 ug/kg) Q2W IV infusion was chosen for monotherapy expansion portion of the ABILITY-1 study. Monotherapy expansion part of ABILITY-1 is enrolling patients with metastatic melanoma, non-melanoma skin cancers (CSCC, MCC, and BCC) and MSI-H/dMMR tumors. The main objectives of the monotherapy dose escalation part of the Phase 1/2 ABILITY-1 study (Clinicaltrials.gov ID: NCT05086692) were to assess MDNA11’s safety, tolerability, PK, PD, and anti-tumor activity to inform on the RDE in an all-comer solid tumor population with advanced cancers refractory to prior systemic therapies. A total of six dose escalation cohorts (MDNA11 dose ranging from 3 ug/kg to 120 ug/kg) were evaluated, with the majority of patients (73%) having also received at least one prior line of immunotherapy with or without primary resistance to immune checkpoint inhibitors. A copy of the poster and a related slide deck have been posted to the “Events and Presentations” page of Medicenna’s website. About MDNA11 MDNA11 is an intravenously administered, long-acting ‘beta-enhanced not-alpha’ interleukin-2 (rIL-2) Superkine specifically engineered to overcome the shortcomings of aldesleukin and other next generation IL-2 variants by preferentially activating immune effector cells (CD8+ T and NK cells) responsible for killing cancer cells, with minimal or no stimulation of immunosuppressive Tregs. These unique proprietary features of the IL-2 Superkine have been achieved by incorporating seven specific mutations and genetically fusing it to a recombinant human albumin scaffold to improve the pharmacokinetic (PK) profile and pharmacological activity of MDNA11 due to albumin’s natural propensity to accumulate in highly vascularized sites, in particular tumor and tumor draining lymph nodes. MDNA11 is currently being evaluated in the Phase 1/2 ABILITY-1 study as both a monotherapy and in combination with pembrolizumab (Keytruda®). About Medicenna Medicenna is a clinical-stage immunotherapy company focused on developing novel, highly selective versions of IL-2, IL-4 and IL-13 Superkines and first in class class-empowered superkines. Medicenna’s long-acting IL-2 Superkine, MDNA11, is a next-generation IL-2 with superior affinity toward CD122 (IL-2 receptor beta) and no CD25 (IL-2 receptor alpha) binding, thereby preferentially stimulating cancer-killing effector T cells and NK cells. Medicenna’s IL-4 Empowered Superkine, bizaxofusp (formerly MDNA55), has been studied in 5 clinical trials enrolling over 130 patients, including a Phase 2b trial for recurrent GBM, the most common and uniformly fatal form of brain cancer. Bizaxofusp has obtained FastTrack and Orphan Drug status from the FDA and FDA/EMA, respectively. Medicenna’s early-stage BiSKITs™ program (Bifunctional SuperKine ImmunoTherapies) is designed to enhance the ability of Superkines to treat immunologically “cold” tumors. Forward-Looking Statements This news release contains forward-looking statements within the meaning of applicable securities laws that relate to the future operations of the Company, plans and projections and other statements that are not historical facts, including, without limitation, statements on the clinical development and potential and safety profile of MDNA11, additional data and reporting thereof. Forward-looking statements are often identified by terms such as “will”, “may”, “should”, “anticipate”, “expect”, “believe”, “seek”, “potentially” and similar expressions and are subject to risks and uncertainties. There can be no assurance that such statements will prove to be accurate and actual results and future events could differ materially from those anticipated in such statements. Important factors that could cause actual results to differ materially from the Company’s expectations include the risks detailed in the latest Annual Report on Form 20-F of the Company and in other filings made by the Company with the applicable securities regulators from time to time in Canada and the United States. The reader is cautioned that assumptions used in the preparation of any forward-looking information may prove to be incorrect. Events or circumstances may cause actual results to differ materially from those predicted, as a result of numerous known and unknown risks, uncertainties, and other factors, many of which are beyond the control of the Company. The reader is cautioned not to place undue reliance on any forward-looking information. Such information, although considered reasonable by management, may prove to be incorrect and actual results may differ materially from those anticipated. Forward-looking statements contained in this news release are expressly qualified by this cautionary statement. The forward-looking statements contained in this news release are made as of the date hereof and except as required by law, we do not intend and do not assume any obligation to update or revise publicly any of the included forward-looking statements. Investor Contact Christina Cameron Investor Relations, Medicenna Therapeutics ir@medicenna.com Argot PartnersPhone: 212-600-1902medicenna@argotpartners.com

WEDNESDAY, July 12, 2023 -- Black men are more likely to die of melanoma, new research shows, and one reason why may be the unusual places where the deadly skin cancer is likely to show up on their bodies. Even though the disease is more common in white men, the new report shows that Black men are 26% more likely to die from it, the Washington Post reported. “The purpose of our study was to dive deeper into why we are seeing these differences in survival rates and the factors that may be driving this,” study co-author Ashley Wysong , chair of dermatology at the University of Nebraska Medical Center, told the Post . The researchers analyzed more than 205,000 cases and discovered that melanoma in Black men is often found in areas that have not had a lot of sun exposure, including the soles of the feet, toes, toenails, fingernails, fingernail beds and palms, the Post reported. About 51% of Black men with melanoma have it on their lower extremities. In white men, only about 10% of those with melanoma have it on their lower extremities, while 35.5% have it on their trunk and nearly 26% have it on their head and neck, the study found. Only about 13% of cases in Black men were on the trunk and just under 10% were on the head. “I think this is significant,” Ali Hendi , a specialist in skin cancer surgery in Chevy Chase, Md., told the Post . “This study doesn’t give us the answer as to why, but it sheds light on the numbers.” Black men also tended to be diagnosed later, with nearly 49% diagnosed at late stages of the disease. Just over 21% of white men are diagnosed with late-stage disease, as are about 40% of Hispanic men, 38% of Asian men and 29% of Native American men, the study found. The findings were published July 11 in the Journal of the American Academy of Dermatology . The five-year survival rate of melanoma is 99% when the cancer is found early, but it’s only 32% after it has spread, the Post reported. That plays out in outcomes, with more than 75% of white men living for five years after diagnosis compared to about 52% of Black men, the study found. The researchers found that about 20% of Black melanoma patients had a deadlier subtype found on the sole of the foot or palm of the hand that is called Acral lentiginous melanoma . Fewer than 1% of white men had this subtype. “It’s not related to sun exposure,” Robert Brodell , a professor of pathology and dermatology at the University of Mississippi Medical Center, told the Post . “It seems to have a different natural history, and a poorer prognosis, though late diagnosis is a component of that.” Wysong noted that melanomas on places like fingers, toes, palms and soles of feet can be mistaken for warts and fungus. “Most people don’t think of skin cancers in their nails or on their hands and feet,” Wysong said. “So we see delays in diagnosis because of the location. It’s hard to see. Most people don’t know what a nail melanoma looks like.” These cancers can look like a black dot under a fingernail, Brodell said. Overall, invasive melanoma cases are up by 27% in 10 years, the Post reported. In 2023, there were over 97,000 cases in the United States, more than 58,000 in men. Nearly 8,000 people are expected to die of melanoma this year. More education is needed for doctors and patients, including in Black patients where it rarely occurs, Jeremy Brauer , a clinical associate professor of dermatology at NYU Langone Health, told the Post . Doctors may not be aware of the differences, Brauer said. “This disproportionate and unfortunate rate of death means we have to try to be much more preventative,” Brauer said. Sources Journal of the American Academy of Dermatology, July 11, 2023 Washington Post Posted July 2023