Squamous cell carcinoma of vulva

Hyloris Broadens Pipeline with new Product Candidate for Vulvar Lichen Sclerosus (VLS) Equal Partnership with AFT Pharmaceuticals for Development of a Drug Releasing Mucoadhesive Film for VLS (HY-091)Limited Availability of Approved Treatment Options in VLS Liège, Belgium – 18 January 2024, 07:00 PM CET – Regulated information – Inside information -Hyloris Pharmaceuticals SA (Euronext Brussels: HYL), a specialty biopharma company committed to addressing unmet medical needs through reinventing existing medications, today announces that it has entered into a partnership with AFT Pharmaceuticals (AFT) to develop a novel mucoadhesive film for the treatment of Vulvar Lichen Sclerosus. HY-091 targets to have an extended duration release of a known molecular entity and to offer a convenient application method, ensuring simplicity and improving compliance. Under the terms of the agreement, Hyloris and AFT will co-develop HY-091 for the purpose of registration and worldwide commercialization. Hyloris is responsible for ensuring the product formulation, manufacturing activities and the coordination of the commercialisation in Europe. AFT is responsible for managing the clinical trials, overseeing all aspects to ensure effective planning, execution and monitoring throughout the trial lifecycle, and the coordination of the commercialisation outside of Europe. Parties are jointly responsible for commercialization in the United States. Stijn Van Rompay, Chief Executive Officer of Hyloris, added: “I am pleased to announce an additional co-development with AFT. This partnership and the recently announced collaboration on HY-090 for Burning Mouth Syndrome are a testament to our shared commitment to making a meaningful impact on the healthcare system. By combining our resources and expertise, we are poised to pioneer innovative solutions for patients suffering from VLS.” About Vulvar Lichen Sclerosus 123Vulvar Lichen Sclerosus (VLS) is a chronic, distressing, inflammatory disease with an enormous impact on quality of life. HY-091 is designed as a user-friendly mucoadhesive film product with a convenient application method that ensures simplicity and compliance, offering targeted relief for patients experiencing the discomfort, itching, and pain associated with Vulvar Lichen Sclerosus by reducing inflammation and scarring in the affected area of skin and helping in restoring the skin structure. There is no curative treatment for VLS, which usually occurs in postmenopausal women, although children and premenopausal women may be affected. Advanced condition severely affects the quality of life and is associated with increases risk of vulvar squamous cell carcinoma.​ It is a massively under diagnosed condition, which affects 0.1% to 3% of the general population. About Hyloris Pharmaceuticals SAHyloris is a specialty biopharma company focused on innovating, reinventing, and optimizing existing medications to address important healthcare needs and deliver relevant improvements for patients, healthcare professionals and payors. The Company’s development strategy primarily focuses on leveraging existing regulatory pathways, such as the FDA’s 505(b)2 pathway in the U.S or similar regulatory frameworks in other region which is specifically designed for pharmaceuticals for which safety and efficacy of the molecule have already been established. This type of regulatory pathway can reduce the clinical burden required to bring a product to market, and significantly shorten the development timelines and reduce costs and risks. Hyloris has built a broad, patented portfolio of 18 reformulated and repurposed value-added medicines that have the potential to offer significant advantages over available alternatives. Two products are currently in early phases of commercialization with partners: Sotalol IV for the treatment of atrial fibrillation, and Maxigesic® IV, a non-opioid post-operative pain treatment. Outside its core strategic focus, the Company also has 1 approved high barrier generic product launched in the U.S. and 2 high barrier generic products in development. Hyloris is based in Liège, Belgium. For more information, visit www.hyloris.com and follow-us on LinkedIn. About AFT Pharmaceuticals LtdAFT is a listed (NZE: AFT) and growing multinational pharmaceutical company that develops, markets, and distributes a broad portfolio of pharmaceutical products across a wide range of therapeutic categories. Its business model is to develop and in-license patented, branded and generic products which are promoted through its dedicated sales teams in Australia, New Zealand and selected Southeast Asian markets, and to out-license its products to local licensees and distributors in over 125 countries around the world. For more information, contact Hyloris:Stijn Van Rompay, CEOStijn.vanrompay@hyloris.com+32 (0)4 346 02 07Jean-Luc Vandebroek, CFOJean-luc.vandebroek@hyloris.com+32 (0)478 27 68 42 Disclaimer and forward-looking statements Hyloris means “high yield, lower risk”, which relates to the 505(b)(2) regulatory pathway for product approval on which the Issuer focuses, but in no way relates or applies to an investment in the Shares.Certain statements in this press release are “forward-looking statements.” These forward-looking statements can be identified using forward-looking terminology, including the words "believes", "estimates," "anticipates", "expects", "intends", "may", "will", "plans", "continue", "ongoing", "potential", "predict", "project", "target", "seek" or "should", and include statements the Company makes concerning the intended results of its strategy. These statements relate to future events or the Company’s future financial performance and involve known and unknown risks, uncertainties, and other factors, many of which are beyond the Company’s control, that may cause the actual results, levels of activity, performance or achievements of the Company or its industry to be materially different from those expressed or implied by any forward-looking statements. The Company undertakes no obligation to publicly update or revise forward-looking statements, except as may be required by law. 1 https://www-uptodate-com.libproxy1.nus.edu.sg/contents/vulvar-lichen-sclerosus-beyond-the-basics2 https://www.jogc.com/article/S1701-2163(21)00890-2/fulltext3 https://www-ncbi-nlm-nih-gov.libproxy1.nus.edu.sg/pmc/articles/PMC5496281/ Attachment 20240118 HY-091-EN_final

MC2 Therapeutics Announces First Patients Enrolled in Phase 2 Proof of Concept Clinical Trial in Vulvar Lichen Sclerosus MC2-25 VLS is a first-in-class drug candidate for urea associated skin diseases using a di-peptide as an iso-cyanate scavenger to inhibit carbamylation of amino acids and proteins in the skinMC2-25 VLS has the potential to become the first approved treatment for Vulvar Lichen Sclerosus (VLS), a debilitating chronic inflammatory disorder thought to affect millions of women globallyPhase 2 proof of concept trial for MC2-25 VLS for VLS will recruit approx. 40 patients across multiple centres with topline results expected in H2 2024 Copenhagen, November 23, 2023 – MC2 Therapeutics, a commercial stage biotech company focused on developing novel treatment paradigms within immune-mediated and inflammatory conditions, today announced that the first patients have been enrolled in a Phase 2 PoC trial evaluating the safety and efficacy of MC2-25 VLS, an innovative new drug candidate for the treatment of urea associated skin diseases, incl. Vulvar Lichen Sclerosus (VLS) where there are no approved treatment options. MC2-25 VLS is a novel treatment paradigm based on a di-peptide that inhibits carbamylation of amino acids and proteins in skin. MC2 Therapeutics believes that carbamylation of amino acids and proteins in the vulvar region by iso-cyanate is the root cause of VLS. MC2-25 VLS has the potential to provide relief from the severe itch, erosions, fissures and pain associated with VLS. This debilitating inflammatory condition is thought to affect millions of patients globally and studies have shown that ~3% of women with VLS eventually develop vulvar squamous cell carcinoma. The Phase 2 clinical trial is being conducted at multiple centres across Denmark and will evaluate the safety and efficacy of MC2-25 VLS in patients with VLS. 40 patients will be recruited for the study and randomized 1:1 in a double-blinded, placebo-controlled parallel-group trial to 12 weeks topical treatment with MC2-25 VLS or placebo. The study is a Phase 2a PoC study. The data generated from this double-blinded, placebo-controlled PoC trial will inform the trial design for a larger Phase 2b trial. “MC2-25 VLS has been developed based on our novel treatment paradigm targeting carbamylation in the skin and the active di-peptide component is formulated using our proprietary PAD Technology™. This delivers a highly attractive treatment profile based on ease of use and tolerability in sensitive, fissured skin,” said Professor Lars Iversen, CMO of MC2 Therapeutics. “As pioneers in uremic diseases, this trial represents a major step forward for MC2 in developing a safe and effective treatment for VLS that severely affects the quality of life of millions of women globally.” Jesper J. Lange, CEO of MC2 Therapeutics said: “Female health remains a hugely underserved area with a distinct lack of approved drugs for female-specific conditions. We are proud to be pioneering MC2-25 VLS for the treatment of VLS as well as for the treatment of Chronic Kidney Disease associated Pruritus in an ongoing Phase 2 trial. In both cases we have the potential to radically change the treatment paradigm for these major indications with huge patient populations, further demonstrating our commitment to changing the immunology and inflammation landscape.” About MC2-25 VLSThe active component of the new drug candidate MC2-25 VLS is a di-peptide, which is formulated in cream based on MC2 Therapeutics’ proprietary formulation and drug delivery system – PAD Technology™. It is highly tolerable in sensitive fissured skin and convenient to use. MC2-25 VLS is an effective isocyanate scavenger showing >90 % inhibition of protein carbamylation and counteracting the morphological skin changes induced by carbamylation as demonstrated in an in vitro reconstructed human uremic skin model. Isocyanate is a very reactive molecule known both to be neurotoxic and to readily react with proteins, peptides and amino acids present in the body and skin. In VLS patients, the vulvar is exposed to iso-cyanate via urine as urea is in equilibrium with iso-cyanate. MC2 Therapeutics believes that carbamylation of amino acids and proteins in the vulvar region by iso-cyanate is the root cause of Vulvar Lichen Sclerosus. About the MC2-25 VLS Phase 2 TrialThe trial is a Phase 2, randomized, multi-centre, double-blinded, placebo-controlled parallel-group trial in subjects with VLS. The trial is expected to enrol 40 patients in multiple centres in Denmark. Patients are randomized 1:1 to either active treatment with MC2-25 VLS or placebo. Subjects will apply trial medication topically for 12 weeks. The primary objective is to explore the efficacy of MC2-25 VLS compared to MC2-25 VLS vehicle in VLS. Secondary objectives are to explore the safety of MC2-25 VLS compared to MC2-25 VLS vehicle in VLS and to explore the burden of VLS on women’s lives. The primary endpoint is mean change in weekly mean Worst Itch Numeric Rating Score (WI-NRS) recorded in the patient’s diary from Baseline to Week 12 for MC2-25 VLS compared to MC2-25 VLS vehicle. Also, secondary endpoints will be assessed, incl. safety and other patient and physician reported outcomes. Topline results are expected in H2 2024. About Vulvar Lichen Sclerosus Vulvar Lichen Sclerosus is a common, chronic, inflammatory, cutaneous disorder that causes severe and distressing itch but also erosions, fissures and pain. It can lead to scarring, impaired sexual function, and malignancy. The true prevalence of VLS is unknown, and probably underestimated as VLS is thought to be underdiagnosed and undertreated (REF: Melnick et al. Int. J Womens Dermatol 2020;6:260-262). While Lichen Sclerosus can affect any area of the body of both males and females, it has a predilection for female anogenital epithelium. The typical VLS patient is a woman around 50 years of age with external genital itch, but it can affect at any age, incl. childhood. Treatment of VLS aims at controlling the symptoms, stopping further scarring and distortion, reducing the risk of cancer and improving the patient’s quality of life (REF: Perez-Lopez FR et al. Climacteric 2017;20:339-347). However, currently there is no approved treatment for VLS in Europe or the US and there is therefore a high unmet medical need for this debilitating disease. About MC2 TherapeuticsMC2 Therapeutics is a commercial stage biotech company focused on developing novel treatment paradigms within immune-mediated and inflammatory diseases. Its innovative approach in immunology is anchored in a deep understanding of skin biology, clinical expertise and cross-silo thinking. Fuelled by an entrepreneurial mindset and creativity, MC2 Therapeutics aims to set new standards in treatment satisfaction for people with immune-mediated and inflammatory conditions.For additional information on MC2 Therapeutics, please visit www.mc2therapeutics.com.Contacts:Lonni Goltermann, +45 2018 1111, investor@mc2therapeutics.com Media: ICR ConsiliumAmber Fennell, +44 20 3709 5700, MC2@consilium-comms.com

LEXINGTON, Mass.--(BUSINESS WIRE)--Agenus Inc. (“Agenus”) (Nasdaq: AGEN), a leader in developing novel immunological agents to treat various cancers, today announced results for the second quarter 2023. Key accomplishments and highlights include: Botensilimab Update: Botensilimab/balstilimab combination data presented at ESMO-GI demonstrated median overall survival (mOS) of 20.9 months and a 23% overall response rate (ORR), both surpassing data reported for standard of care in 3L+ Non-MSI-H colorectal cancer (CRC) in patients without active liver metastases. Regulatory: The U.S. FDA granted Fast Track designation for the botensilimab/balstilimab combination in 3L+ Non-MSI-H CRC in patients without active liver metastases. Agenus is exploring global accelerated approval strategies for CRC. Clinical Trial Progress: Ongoing Phase 2 ACTIVATE trials in CRC and melanoma expected to fully enroll by end of year. AGEN2373 Update: AGEN2373 Phase 1 dose escalation data presented at ASCO demonstrated promising monotherapy clinical responses in patients with advanced solid tumors. “Botensilimab, alone or in combination with balstilimab, continues to display remarkable clinical activity in over 600 patients treated across nine late-stage, treatment resistant solid tumor cancers, demonstrating great potential to revolutionize the role of immunotherapy in cancer treatment,” said Chief Executive Officer, Garo Armen, Ph.D. “Agenus is committed to advancing our diverse clinical pipeline with a focus on expediting our first regulatory submission for the botensilimab/balstilimab combination in colorectal cancer. Our data has demonstrated an unprecedented survival benefit over what has been reported for standard of care, underscoring this combination as an important potential treatment option for patients with non-MSI-high colorectal cancer, which represents 85% of the population of patients with colorectal cancer1.” Botensilimab/Balstilimab (“Bot/Bal”) Combination in 3L+ Non-MSI-H Metastatic CRC Data Presented at the ESMO-GI World Congress on Gastrointestinal Cancer in June 2023: In 69 evaluable patients with non-MSI-High CRC without active liver metastases, results demonstrated a meaningful improvement over standard of care in both overall response rate (ORR%) and median overall survival (mOS): mOS of 20.9 months as compared to the recently reported 12.9-month benchmark with standard care.2 ORR of 23% as compared to the recently reported 2.8%1 benchmark with standard care. In April 2023, the U.S. FDA granted Fast Track designation to the bot/bal combination for patients with non-MSI-H/dMMR metastatic CRC without active liver metastases. The ACTIVATE Phase 2 trial in this patient population is on target to conclude enrollment by year-end. Planning is underway for a Phase 3 CRC study; with Fast Track designation from the FDA, study design and timing will be determined as we discuss our filing approach with the agency. A Biologics License Application to the FDA is planned in 2024. Botensilimab in Other Advanced Solid Tumor Cancers: Lung: Enrollment continues for a Phase 1b trial targeting PD-(L)1 +/- chemotherapy relapsed/refractory non-small-cell lung cancer (NSCLC); data update planned by year-end. Melanoma: Ongoing global enrollment in Phase 2 ACTIVATE trial with data update planned in 2024. Ovarian: Phase 1b trial in patients with platinum-resistant ovarian cancer (PROC) demonstrated a 33% ORR and 67% disease control rate among primarily high-grade, heavily pretreated patients (presented at SGO in March 2023). Sarcomas: Updated data for a Phase 1b cohort with advanced sarcomas to be presented at ESMO on October 21st 2023. AGEN2373 Data Presented at the ASCO 2023 Annual Meeting: Complete results from the first-in-human monotherapy dose escalation study of AGEN2373, a CD137 agonist, in patients with advanced solid tumors: Reported responses in metastatic prostate cancer, ampullary carcinoma, and vulvar squamous cell carcinoma highlight the potential impact of AGEN2373. AGEN2373 is the first CD137 agonist antibody to report single-agent responses with no major toxicities. Clinical data are consistent with mechanistic design intent of AGEN2373 to avoid hepatic toxicity, a typical constraint of CD137-targeted agonists. Leadership Appointments: In alignment with Agenus' next phase of growth and anticipated commercialization of the bot/bal combination, the company announced the following key executive appointments: Robin Taylor, Ph.D., Chief Commercial Officer. Homa Yeganegi, Chief Product Strategy and Global Medical Affairs Officer. Stephanie Fagan, Chief Communications Officer. Second Quarter 2023 Financial Results: We ended our second quarter 2023 with a cash, cash equivalent and short-term investment balance of $157.6 million, compared to $193.4 million at December 31, 2022. In addition, we have raised $20.3 million through sales of our common stock under our at market issuance sales agreement since the end of Q2 2023. For the three and six months ended June 30, 2023, we recognized revenue of $25.3 million and $48.2 million and incurred a net loss of $73.4 million and $144.3 million, respectively. Our net loss includes non-cash expenses of $28.9 million for the three months ended, and $53.8 million for the six months ended, June 30, 2023. Select Financial Information (in thousands, except per share data) (unaudited) June 30, 2023 December 31, 2022 Cash, cash equivalents and short-term investments $ 157,852 $ 193,358 Cash raised since quarter end $ 20,281 Three months ended June 30, Six months ended June 30, 2023 2022 2023 2022 Revenues, royalty sales milestone $ - $ 17,316 $ - $ 17,316 Revenues, non-cash royalty 22,068 144 41,174 17,778 Revenues, research and development 2,489 1,907 5,101 8,647 Revenues, other 739 1,559 1,923 3,126 Total Revenue 25,296 20,926 48,198 46,867 Research and development expenses 59,285 44,960 116,402 87,404 General and administrative expenses 20,415 18,914 38,653 37,866 Cost of service revenue 254 2,024 2,548 2,567 Other income (883 ) (8,966 ) (1,604 ) (8,776 ) Non-cash interest expense 19,647 13,636 36,920 28,588 Non-cash contingent consideration fair value adjustment 8 (407 ) (398 ) (943 ) Net loss* $ (73,430 ) $ (49,235 ) $ (144,323 ) $ (99,839 ) Net loss per share attributable to Agenus Inc. common stockholders: $ (0.20 ) $ (0.17 ) $ (0.41 ) $ (0.35 ) *Includes non-cash expenses Adjusted Net loss for non-cash expenses: Net loss as reported $ (73,430 ) $ (49,235 ) $ (144,323 ) $ (99,839 ) Non-cash expenses Depreciation and amortization 2,973 1,690 5,535 3,350 Share based compensation 6,042 4,634 11,527 9,625 Non-cash interest expense 19,647 13,636 36,920 28,588 Other 285 (409 ) (100 ) (943 ) Total non-cash expenses 28,947 19,551 53,882 40,620 Net loss excluding non-cash expenses $ (44,483 ) $ (29,684 ) $ (90,441 ) $ (59,219 ) References 1 2 Cohen et al. ASCO Annual Meeting 2023 About Botensilimab Botensilimab, an investigational multifunctional CTLA-4 antibody, is designed to extend immunotherapy benefits to “cold” tumors, which have not historically responded to standard of care or other investigational therapies. Besides binding to the CTLA-4 receptor, its Fc-enhanced structure induces a memory immune response, downregulates regulatory T cells, and activates T cells, thereby enhancing immune responses. Approximately 600 patients have been treated with botensilimab in phase 1 and phase 2 clinical trials. Botensilimab alone, or in combination with Agenus’ PD-1 antibody, balstilimab, has shown clinical responses across nine metastatic, late-line cancers. For more information about botensilimab trials, visit with the identifiers NCT03860272, NCT05608044, NCT05630183, and NCT05529316. About AGEN2373 AGEN2373 is a novel anti-CD137 agonist that has been designed to activate T and NK cells while mitigating liver toxicities common to the CD137 target class. CD137 (4-1BB) is an activating receptor expressed on T and NK cells. Upon binding to CD137, AGEN2373 is designed to stimulate the growth and activation of cytotoxic T and NK cells, triggering a lasting memory response to cancer. AGEN2373 binds to a unique epitope designed to achieve this response specifically within the tumor microenvironment. This selective binding is designed to avoid serious side effects associated with CD137 activation in the liver that have been reported by competitor molecules. AGEN2373 has demonstrated preliminary clinical activity and has been well tolerated by patients without signs of liver toxicity (Barve et al. ASCO 2023). About Agenus Agenus is a leading immuno-oncology company targeting cancer and infectious diseases with a comprehensive pipeline of immunological agents. The company’s mission is to expand patient populations benefiting from cancer immunotherapy through combination approaches, using a broad repertoire of antibody therapeutics, adoptive cell therapies (through MiNK Therapeutics) and adjuvants (through SaponiQx). Agenus is headquartered in Lexington, MA. For more information, visit or follow us on LinkedIn and Twitter @agenus_bio. Non-GAAP Financial Measures To supplement our financial disclosures that are prepared and presented in accordance with generally accepted accounting principles in the United States (“GAAP”), this press release includes Adjusted Net Loss, which is a non-GAAP financial measure that we believe is helpful to our investors. We use these non-GAAP financial measures for financial and operational decision-making purposes. We believe these measures provide investors with meaningful period-to-period comparisons of our underlying performance. Adjusted Net Loss is a supplemental measure of our operating performance and excludes the impacts of certain costs required to be recorded under GAAP. We calculate Adjusted Net Loss as net loss adjusted to exclude non-cash expenses of depreciation and amortization, share based compensation, non-cash interest expense and certain other non-cash expenses. Accordingly, Adjusted Net Loss should not be considered in isolation or as a substitute for net loss, which is the most directly comparable financial measure presented in accordance with GAAP. Forward-Looking Statements This press release contains forward-looking statements that are made pursuant to the safe harbor provisions of the federal securities laws, including statements relating to our technologies, therapeutic candidates, and capabilities, for instance, statements regarding therapeutic benefit and efficacy, mechanism of action, potency, durability, and safety and tolerability pro our therapeutic candidates, both alone and in combination with each other and/or other agents; statements regarding future plans, including research, clinical, regulatory, and commercialization plans; and any other statements containing the words "may," "believes," "expects," "anticipates," "hopes," "intends," "plans," "will" and similar expressions are intended to identify forward-looking statements. These forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially. These risks and uncertainties include, among others, the factors described under the Risk Factors section of our most recent Quarterly Report on Form 10-Q or Annual Report on Form 10-K filed with the Securities and Exchange Commission and available on our website: . Agenus cautions investors not to place considerable reliance on the forward-looking statements contained in this release. These statements speak only as of the date of this press release, and Agenus undertakes no obligation to update or revise the statements, other than to the extent required by law. All forward-looking statements are expressly qualified in their entirety by this cautionary statement.