CD40

Published in the Journal for ImmunoTherapy of Cancer (JITC), Intravenous Dosing Shows Strong Evidence of Tumor Delivery, Viral Replication and Transgene Expression CAMBRIDGE, Mass.--(BUSINESS WIRE)--Akamis Bio, a clinical-stage oncology company using a proprietary Tumor-Specific Immuno-Gene Therapy (T-SIGn®) platform to deliver novel immunotherapeutic proteins, biomolecules and transgene combinations to treat solid tumors, today announced the publication of data supporting the continued clinical development and intravenous route of administration of NG-350A, its lead program for the treatment of advanced metastatic cancers. NG-350A is a next-generation transgene-armed tumor gene therapy designed to drive intratumoral expression of a CD40 agonist monoclonal antibody resulting from selective replication in both primary and metastatic epithelial-derived solid tumors. Data from the first-in-human dose escalation FORTITUDE study in patients with metastatic/advanced epithelial tumors supports proof-of-mechanism for NG-350A, with strong evidence of tumor-selective delivery, replication and transgene expression. Additionally, this study demonstrates that intravenous delivery of NG-350A results in a superior overall pharmacokinetic and pharmacodynamic profile, with no apparent disadvantages versus intratumoral injection. Blood sample analysis from patients showed sustained persistence of NG-350A up to seven weeks after intravenous dosing was completed (maximum follow up), particularly at higher dose levels. Further, a dose-dependent pattern was also seen with systemic delivery, resulting in four patients remaining positive for vector DNA in biopsies nearly two months after receiving the treatment. Transgene messenger RNA from replicating NG-350A was detected in nearly half the patients with intravenous treatment but only in one patient that had received intratumoral injection. Sustained increases in inflammatory cytokines were also observed following dosing, particularly with higher intravenous dose levels. “These findings are highly supportive of our ongoing focus on intravenous administration of NG-350A to safely drive sustained transgene expression within the tumor microenvironment. Systemic delivery offers considerable advantages over current intratumoral approaches, particularly with transgene-containing viral vectors where the cargo needs to reach both the primary tumor and metastases throughout the body – an application for which direct injection or dependence on an abscopal effect is not viable,” said Oliver Rosen, M.D., Chief Medical Officer at Akamis. Dr. Rosen continued: “This study demonstrated that a T-SIGn therapeutic armed with targeted immunostimulatory proteins such as CD-40 agonists can be successfully delivered intravenously, resulting in a superior overall pharmacokinetic and pharmacodynamic pro to intratumoral administration. Our preliminary data suggest that the local expression of immunostimulatory therapies following intravenous administration can overcome toxicity that limits non-targeted systemic administration. We look forward to continuing to understand the potential of this treatment in upcoming proof-of-concept studies.” NG-350A will now be studied in combination with chemoradiotherapy in FORTRESS, a multicenter open-label non-randomized Phase 1b trial of patients with locally advanced rectal cancer. A link to the publication “First-in-human clinical outcomes with NG-350A, an anti-CD40 expressing tumor-selective vector designed to remodel immunosuppressive tumor microenvironments” can be found here. About T-SIGn Akamis Bio’s T-SIGn® therapeutics are based on a replication competent, chimeric group B adenovirus backbone which has been adapted via directed evolution to home specifically to both primary and metastatic epithelial-derived solid tumor tissue following intravenous delivery. Once at the tumor site, T-SIGn therapeutics can drive the intratumoral expression of multiple transgene payloads, turning solid tumor cells into “drug factories” while leaving healthy tissue unaltered and intact. The intratumoral expression of immunologically active biomolecules and therapeutic proteins can result in the remodeling of the solid tumor microenvironment, triggering robust antitumor immune responses. T-SIGn therapeutics have the potential to be used in the monotherapy setting, as well as in combination with other immuno-oncology agents to target the key mechanisms that tumors use to evade the immune system. About Akamis Bio Akamis Bio is a clinical-stage oncology company using a proprietary Tumor-Specific Immuno-Gene Therapy (T-SIGn®) platform to deliver novel immunotherapeutic proteins, biomolecules and transgene combinations to treat solid tumors. The company is developing a portfolio of solid tumor-targeted T-SIGn therapeutics which aim to enable a patient’s own immune system to recognize, attack, and clear their cancer. Akamis Bio has a growing pipeline of T-SIGn therapeutics anchored by its lead clinical-stage program, NG-350A (an immuno-stimulatory tumor gene therapy driving intratumoral expression of a CD40 agonist monoclonal antibody) being investigated in ongoing Phase 1 clinical studies in patients with metastatic or advanced epithelial tumors. In addition to internal pipeline development efforts, Akamis Bio has a number of T-SIGn platform-focused collaborations with leaders in the immuno-oncology field including Merck and the Cancer Research Institute (CRI). To learn more, please visit . Contacts Media: Jason Glashow Glashow Strategic Communications Jason.Glashow@akamisbio.com

PRESS RELEASE Results from a Phase I clinical trial of a dendritic cell targeting prophylactic HIV vaccine published in the Journal eClinical Medicine Provides important validation of the safety and immunogenicity of EnnoDC’s technology The ANRS VRI06 trial, carried out by Inserm, ANRS MIE and the VRI, shows that the CD40.HIVRI.Env vaccine, is safe and induces early and sustained humoral and cellular immune responses against HIVThe first clinical trial results in humans with this novel type of vaccine, which consists of a monoclonal antibody fused to the HIV envelope, targeting the CD40 molecule expressed at the surface of dendritic cellsResults were published in the Journal eClinical Medicine, an open access clinical journal, published by The Lancet Paris, France, 2 October 2024 – EnnoDC* (or “the Company”), a clinical-stage biotech company pioneering the development of first-in-class dendritic cell-targeting immunotherapies, today notes the publication of positive results from a Phase I trial of its novel Dendritic Cell (DC) targeting prophylactic HIV vaccine in the Journal eClinical Medicine, an open access clinical journal, published by The Lancet. The multicentre, double-blind placebo-controlled dose-escalation trial was conducted at clinical sites in France and Switzerland. The results, published by scientists from the Vaccine Research Institute of Inserm and the Université Paris-Est Créteil, the CHUV in Lausanne and the University of Bordeaux, show that the vaccine, CD40.HIVRI.Env, is safe and induces early and sustained humoral and cellular immune responses against HIV. No serious side effects were observed. General and local reactions at the injection site were mainly mild to moderate. Two severe adverse events were reported, which were found to be unrelated to vaccination after analysis. EnnoDC’s first-in-class approach combines the power of vaccines and immunotherapies to provide targeted immune responses for both cancer and infectious diseases. CD40.HIVRI.Env combines a humanized anti-CD40 monoclonal antibody fused with HIV envelope antigens to stimulate DCs through CD40 and deliver a targeted immune response. Pr. Yves Lévy, co-founder, Chief Medical and Scientific Officer at EnnoDC and Principal Investigator of the trial commented: “These are exciting results for EnnoDC from the first clinical study using our novel dendritic cell targeting technology. The results show that this vaccine is safe and well tolerated and that humoral and cellular immune response were activated against HIV. The results support further development of the program. In addition, the results show that this type of treatment, which specifically targets antigens to the dendritic cells via the CD40 molecule, may be potent in inducing protective immunological responses in prime-boost vaccination strategies.” Christophe Hubert, Chief Executive Officer of EnnoDC, added: “These are very encouraging results which provide further validation of our technology with positive read across to our new immunotherapies, in development for HPV-induced cancers, prostate cancer and infectious diseases.” Last week EnnoDC unveiled the next generation of DC-targeting immunotherapies supported by new leadership and an evolved strategy. EnnoDC has an extensive pipeline of clinical and preclinical stage assets in HPV-induced cancers, prostate cancer and in infectious diseases. Further information on the ANRS VRI06 trial is available in a press release issued by the Vaccine Research Institute (VRI) of Inserm and the Université Paris-Est Créteil (Unit 955 Mondor Institute for biomedical research), the CHUV in Lausanne and the University of Bordeaux through the link below:Preventive vaccine against HIV: promising results in healthy volunteers with a new vaccine technology – Vaccine Research Institute (vaccine-research-institute.fr) The full paper, published in the October 2024 issue of eClinical Medicine, can be accessed through the following link: https://doi.org/10.1016/j.eclinm.2024.102845. Further details about the trial can be found online at https://clinicaltrials.gov/study/NCT04842682. *EnnoDC is the trading name of LinKinVax Europe SAS. -Ends- For more information please contact: EnnoDC Christophe Hubert, CEOinfo@EnnoDC.com ICR Consilium Ashley Tapp / Jonathan Edwards / Kumail Waljee EnnoDC@consilium-comms.comTel: +44 (0) 20 3709 5700 About EnnoDC EnnoDC, the trading name of LinKinVax, is a clinical-stage biotech company pioneering the development of first-in-class Dendritic Cell (DC)-targeting immunotherapies. Through our versatile DC-targeting immunotherapy platform we are developing CD40-specific monoclonal antibodies fused with pathogenic antigens to induce a highly specific, safe, broad, and long-lasting immune response to combat diseases like cancer and infectious diseases. The Company currently has three active clinical trials in various stages of clinical development, addressing oncology and infectious disease indications. Its lead asset, CD40HVac is currently in a Phase I/IIa clinical trial for HPV16+ oropharyngeal cancer patients. EnnoDC is a spin out from the Vaccine Research Institute (VRI), an institute of INSERM (the French National Institute of Health and Medical Research) and is supported by longstanding investors and internationally renowned key opinion leaders who contribute their expertise in the clinical development of EnnoDC’s assets and help explore the expansive therapeutic potential of its innovative platform. Find out more online at: http://www.EnnoDC.com Follow us on X and LinkedIn About ANRS MIEANRS Emerging Infectious Diseases is an autonomous agency of Inserm (the French National Institute for Health and Medical Research). Its mission is to facilitate, evaluate, coordinate and fund research into HIV/AIDS, viral hepatitis, sexually transmitted infections, tuberculosis and emerging and re-emerging infectious diseases. For more information: https://anrs.fr/en/ About the VRI and Inserm The Vaccine Research Institute (VRI), Laboratory of excellence, was established by Inserm (French National Institute of Health and Medical Research) and the University of Paris-Est Créteil (UPEC) to conduct research to accelerate the development of effective vaccines against HIV/AIDS and (re)-emerging infectious diseases. The VRI's structure strengthens the links between basic research and translational research, patient associations and the socio-economic world. The VRI extends a network of internationally renowned scientists and research teams with multidisciplinary expertise in system biology and clinical immunology, a network of clinical centres, and shared platform.For more information: https://vaccine-research-institute.fr/ Founded in 1964, Inserm is a public scientific and technological institute dedicated to biomedical research and human health and is involved in the entire range of activities from the laboratory to the patient’s bedside. It also partners with the most prestigious research institutions in the world that are committed to scientific challenges and progress in these fields.For more information: https://www.inserm.fr/en/home/ About Université Paris-Est Créteil: With 14 faculties, schools and institutes, 1 observatory and 32 research laboratories, Université Paris-Est Créteil has been active in all fields of knowledge since 1970. Each year, UPEC trains over 42,000 students and working professionals of all ages. A major player in the dissemination of academic, scientific and technological knowledge, the university offers more than 500 training courses in all disciplines and at all levels. UPEC offers personalized support for all successes, thanks to undergraduate and graduate training, recognition of prior learning and lifelong learning opportunities. Furthermore, the university runs a growing number of apprenticeship programs in order to stimulate entrepreneurship and ease professional integration. Université Paris-Est Créteil has built its strategic plan around three strategic orientations: UPEC is an engaged university that aims to match academic excellence with societal relevance. It encourages and supports all paths of students’ success with dedicated programs. UPEC masters its trajectory and is a university open to the world and its diversity. For more information: https://www.en.u-pec.fr/ About the University of Bordeaux With more 54,000 students, 3,200 researchers and teachers, and 2,800 staff members, the University of Bordeaux is one of the leading French public research and higher education institutions, located in a dynamic and culturally rich, fast-developing region. Ranked among the top universities in France, the University of Bordeaux is renowned for the quality of its academic courses and research. It is a multi-disciplinary, research-focused institution with a strong ambition to develop as a leading, international campus. The University of Bordeaux is leading an ambitious, competitive development program in partnership with local higher education institutes and national research organizations, in order to promote Bordeaux as a “Campus of Excellence”. For more information: https://www.inserm.fr/en/home/

iStock, Polinmr As traditional fundraising methods falter for smaller firms, the rise of royalty deals is reshaping how companies access capital, offering an alternative that bypasses equity dilution and debt. The environment for biotech and smaller pharma companies to raise capital has been difficult in recent years. Investor confidence in the biotech industry has struggled since the highs seen during the pandemic, with the XBI index of stocks remaining largely flat over the last two years. Though there are signs that 2024 represents a resurgence in investment , with IPOs and M&A activity surpassing levels seen in 2023, the industry is still recovering from the flight of capital. Life science companies have reacted to the difficulty in sourcing capital in various ways, such as the broad industry move to downsize and restructure workforces to extend available cash reserves and a trend for companies to delay potential IPOs . In the background of such strategies, there has been a shift to an alternative option for sourcing capital, through royalty financing. Though they have been around for decades, royalty deals are a means of raising capital that involves an investor buying a percentage of future revenue from a drug manufacturer on specific single or multiple assets. In this way, a manufacturer can receive an upfront fee and potentially future milestone payments dependent on the development of the asset, which can then be used for short-term capital needs. This type of financing is distinct from an equity deal because it offers the company a non-dilutive means of raising funds for development or commercialization costs. It can also be a more flexible arrangement than taking on debt because there are no interest payments to meet nor is the deal itself dependent on the economic environment. The latter advantage is one of the major reasons that this type of deal is on the rise and why more can be expected in the future. George Shuster Jr., partner at law firm WilmerHale, told BioSpace that the number of such deals has grown “exponentially” in the last three years, following a steady increase over the last decade. WilmerHale earlier this month released an analysis of the surge in royalty financing in the “difficult” life sciences fundraising environment. “As royalty financing and monetization transactions gain momentum as alternatives to traditional debt and equity financing, life sciences companies may look to take advantage of these methods of fundraising to accelerate product development, launch clinical programs, or acquire additional assets,” the report found. Twin Drivers for Deals Previously, these types of deals were considered highly specialized transactions that only fit a narrow set of circumstances, according to Shuster. However, with the entry of a greater number of private credit investment funds, there has been more interest in creating novel transactions to expand their portfolios and to meet demand for capital, he said. In convergence with the rise of private investment has been the downturn in the overall market environment for supporting smaller companies and biotechs. Not surprisingly, royalty financing is a popular option for emerging biopharma. “The market for life sciences companies in equity transactions has slowed down to a point of all but drying up—not just at the IPO level, but really all the way down to much earlier stage financings,” Shuster explained. “And as that happened, the stock price for public life sciences companies has suffered. That means not only is it harder to get the equity financing in the door, but if you are going to raise equity financing, it is at very unattractive prices that would be extremely dilutive to the existing shareholders.” For companies seeking to complete royalty financings, part of the appeal is being able to raise capital without having to dilute existing shareholders, especially at the later stages of developing a product. For the investors, it is attractive to have a return from such deals that is not dependent on the stock market or interest rates, with the profit driven instead by the success of the product at the heart of the deal, according to Nathan Moore, partner at WilmerHale. As a result, the number and scale of such deals is increasing, with Royalty Pharma—a specialist buyer of royalties— striking deals potentially worth close to $2 billion in May 2024 alone. In one of those deals, Royalty Pharma paid $525 million to acquire the royalties and milestones for ImmuNext’s anti-CD40 therapy frexalimab, which is currently in Phase III trials for multiple sclerosis. In return, Royalty will receive 100% of annual worldwide net royalties that ImmuNext would have received under its licensing deal with Sanofi, up to $2 billion. In a report based on 2022 data, management consulting firm ZS found that over the preceding four years, the average value of royalty deals increased more than twice as fast compared with other financing types, with the total value of royalty deals growing at a compound annual growth rate of 45%, compared with 25% for equity deals. “This suggests greater resilience against the macroeconomic factors impacting today’s equity market,” ZS concluded. Big Pharma on Sidelines Traditionally, it has been Big Pharma stepping in to snap up the rights to assets that are closing in on commercialization. Private investment companies entering into the market to swoop for these potential products would seem to be encroaching on this territory. Any products that proved to have potential in key therapeutic areas would then have a less attractive revenue potential for any would-be buyers. Shuster instead suggested that Big Pharma has been happy to take a backseat and allow other companies to take a risk in the short term, permitting private investments to fill the financial hole needed to get assets over the line. In this way, there is less pressure for Big Pharma to spread its investments across too many assets, and they still retain the opportunity to swoop in to acquire the company or product should it prove to be successful. With the economic environment being such a driver for these royalty deals, the question remains as to whether this trend will continue if the market becomes more friendly to traditional forms of investment. While a more open equity market could potentially see the need for this type of investment reduced, Shuster contends that it would not see completely disappear as a financing option. “This investment product will be sustained at levels above where it used to be because now there is a group of lenders who know how to do these transactions, and who know the pros and cons of these transactions,” Shuster concluded. “These companies know how to fit this in with other equity and debt financing strategies that they may have—once you have the tool in the toolbox, you’re going to continue to use it.”