CCL19

Researchers have shown that sleep enhances the migratory potential of T cells toward lymph nodes. Researchers at LMU Munich have shown that sleep enhances the migratory potential of T cells toward lymph nodes. Sleep is healthy -- this popular knowledge is backed by science. Previous research had already shown that in people who slept after a vaccination, the immune response was twice as strong on average as in people who did not sleep during the night after the vaccination. However, the cell biological reasons for this had been little investigated before now. A team led by Professor Luciana Besedovsky from the Institute of Medical Psychology has now demonstrated that sleep promotes the potential of immune cells -- so-called T cells -- to migrate toward lymph nodes. The researchers have reported their findings in the journal Brain, Behavior, and Immunity. Significant differences after sleepless night The scientists repeatedly examined the concentration of various subgroups of T cells in the blood of a cohort of healthy men and women over the course of two 24-hour sessions. In one of the two test conditions, the participants were allowed to sleep at night for eight hours, while in the other they relaxed in bed at night but stayed awake. A forearm catheter connected to an adjacent room by means of a tube enabled blood collection without disturbing the participant's sleep. Analysis of the blood samples revealed significant differences between the test conditions: "Our results show that sleep promotes the migratory potential of various T-cell subpopulations," says Besedovsky. Migration of T cells toward lymph nodes As the researchers demonstrated, sleep increases the directed migration of T cells toward a signaling protein, the so-called 'homing' chemokine CCL19. This molecule mediates the migration of T cells, which possess the corresponding receptor for CCL19, to the lymph nodes, where the T cell immune defenses are 'trained' by being presented with antigens -- for example, after a vaccination. In further experiments, the researchers showed that incubating T cells with blood plasma taken from sleeping participants likewise increased the migratory potential. "This demonstrates that soluble factors that are elevated in blood plasma during sleep mediate the effect of sleep on T-cell migration. So we can in a way recreate the effect of sleep in the lab using the blood plasma of sleeping persons," reports Besedovsky. The scientists identified growth hormone and prolactin as the decisive factors for this migration behavior. Both hormones showed sleep-dependent changes in concentration in the plasma, with higher values among the participants who slept during the night. "Our results also have potential clinical implications," says Besedovsky. "Thus, growth hormone and prolactin could be considered as new adjuvants to promote immune responses following vaccination, especially in aged people, who typically display reduced levels of these hormones during sleep." Overall, the authors see the study as an important step for better understanding why sleep supports immune responses -- for example, after vaccination -- and why vaccines are often less effective in older people.

When fighting disease, our immune cells need to reach their target quickly. Researchers have now discovered that immune cells actively generate their own guidance system to navigate through complex environments. This challenges earlier notions about these movements. The researchers' findings enhance our knowledge of the immune system and offer potential new approaches to improve human immune response. When fighting disease, our immune cells need to reach their target quickly. Researchers at the Institute of Science and Technology Austria (ISTA) now discovered that immune cells actively generate their own guidance system to navigate through complex environments. This challenges earlier notions about these movements. The researchers' findings, published in the journal Science Immunology, enhance our knowledge of the immune system and offer potential new approaches to improve human immune response. Immunologic threats like germs or toxins can arise everywhere inside the human body. Luckily, the immune system -- our very own protective shield -- has its intricate ways of coping with these threats. For example, a crucial aspect of our immune response involves the coordinated collective movement of immune cells during infection and inflammation. But how do our immune cells know which way to go? A group of scientists from the Sixt group and the Hannezo group at the Institute of Science and Technology Austria (ISTA) addressed this question. In their study, published today in Science Immunology, the researchers shed light on the immune cells' ability to collectively migrate through complex environments. Dendritic cells -- The Messengers Dendritic cells (DCs) are one of the key players in our immune response. They function as a messenger between the innate response -- the body's first reaction to an invader, and the adaptive response -- a delayed reaction that targets very specific germs and creates memories to fight off future infections. Like detectives, DCs scan tissues for intruders. Once they locate an infection site, they are activated and immediately migrate to the lymph nodes, where they hand over the battle plan and initiate the next steps in the cascade. Their migration towards the lymph nodes is guided by chemokines -- small signaling proteins released from lymph nodes -- that establish a gradient. In the past, it was believed that DCs and other immune cells react to this external gradient, moving along towards a higher concentration. However, novel research conducted at ISTA now challenges this notion. One receptor -- two functions The scientists took a close look at a receptor -- a surface structure found on activated DCs called "CCR7." CCR7's essential function is to bind to a lymph node-specific molecule (CCL19), which triggers the next steps of the immune response. "We found that CCR7 not only senses CCL19 but also actively contributes to shaping the distribution of chemokine concentrations," Jonna Alanko, a former postdoc from the lab of Michael Sixt, explains. Using different experimental techniques, they demonstrated that as DCs migrate, they take up and internalize chemokines via the CCR7 receptor, resulting in local depletion of chemokine concentration. With less signaling molecules around, they move further into higher chemokine concentrations. This dual function allows immune cells to generate their own guidance cues to orchestrate their collective migration more effectively. Movement depends on cell population To understand this mechanism quantitatively at the multicellular scale, Alanko and colleagues teamed up with theoretical physicists Edouard Hannezo and Mehmet Can Ucar, also at ISTA. With their expertise in cell movement and dynamics, they established computer simulations that were able to reproduce Alanko's experiments. With these simulations, the scientists predicted that the dendritic cells' movement not only depends on their individual responses to the chemokine but also on the density of the cell population. "This was a simple but nontrivial prediction; the more cells there are the sharper the gradient they generate -- it really highlights the collective nature of this phenomenon!" says Can Ucar. Additionally, the researchers found that T-cells -- specific immune cells that destroy harmful germs -- also benefit from this dynamic interplay to enhance their own directional movement. "We are eager to find out more about this novel interaction principle between cell populations with ongoing projects," the physicist continues. Enhancing the immune response The discoveries are a step in a new direction for how cells move inside our bodies. In contradiction to what was previously believed, immune cells not only respond to chemokines, but they also play an active role in shaping their own environment by consuming these chemical signals. This dynamic regulation of signaling cues provides an elegant strategy to guide their own movement and that of other immune cells. This research has significant implications for our understanding of how immune responses are coordinated within the body. By uncovering these mechanisms, scientists could potentially design new strategies to enhance immune cell recruitment to specific sites, such as tumor cells or areas of infection.

Full read-out of the Phase 1/2a trial of EVX-02 in 10 patients with completely resected melanoma was presented at AACR in April 2023, meeting primary endpoints and demonstrating relapse-free survival in all EVX-02 completers Recent R&D Day highlighted Evaxion´s proprietary genetic adjuvant technology enhancing efficacy of DNA and mRNA vaccines Announcement of novel AI-platform for identification of a new source of therapeutic targets, ERVs (endogenous retroviruses), potentially enabling treatment of patients that are currently considered unresponsive to cancer immunotherapy Full read-out of the Phase 1/2a trial of EVX-01 in 12 patients with metastatic melanoma will be presented at the American Society for Clinical Oncology (ASCO) Meeting in June 2023 Cash and cash equivalents of $10.2 million at March 2023 sufficient to fund operations into early December 2023 COPENHAGEN, Denmark, May 31, 2023 (GLOBE NEWSWIRE) -- Evaxion Biotech A/S (NASDAQ: EVAX) (“Evaxion” or the “Company), a clinical-stage biotechnology company specializing in the development of AI-driven immunotherapies, announced today its first quarter 2023 financial results and provided a business update. “Evaxion continues to make significant progress towards our mission of advancing AI-powered immunotherapies to save lives,” said Per Norlén, Chief Executive Officer of Evaxion. “Data, reported at AACR 2023 and to be presented at ASCO 2023, show that in our trials in melanoma with EVX-02 and EVX-01, respectively, patients experienced promising clinical responses, with good overall tolerability. These data provide important validation for Evaxion’s AI-driven approach to personalized cancer vaccines and underscore our enthusiasm for our next-generation vaccine candidate, EVX-03, slated to begin clinical trials by the end of this year.” “We have also announced important advances in our proprietary AI-technology, including the new platform ObsERV™, which enables Evaxion to identify new patient-specific tumor targets, called ERVs, based on ancient viral remnants in our genome. It has the potential to further enhance the efficacy of our personalized cancer vaccine EVX-03, as well as broadening immunotherapy to patients that are currently unresponsive to such treatments” said Per, concluding, “We believe that the promising clinical data from our first-generation programs and the exciting technology advancement with our genetic adjuvant technology, position Evaxion at the forefront of the recent resurgence in interest for nucleic acid-based vaccines.” Anticipated milestones June 2023 - Full readout of EVX-01 Phase 1/2a trial at ASCO Q3 2023 - CTA filing for EVX-03* Q4 2023 – Interim results of EVX-01 Phase 2 trial in melanoma Q4 2023 – Initiate enrollment of EVX-03 Phase 1 trial* *Subject to additional funding in the range of $ 5-10 million Promising clinical data presented for EVX-01 and EVX-02 Clinical readout for the Phase 1/2a trial of EVX-02 was presented at AACR in April. All 10 patients with late stage melanoma who completed EVX-02 treatment demonstrated robust and treatment-specific immune responses and were relapse-free at their last assessment. EVX-01 will be presented at ASCO on June 3. The overall outcome of the trial was made public on May 25 with positive clinical responses in 8 out of 12 patients receiving EVX-01 in combination with a checkpoint inhibitor. The trial also met primary endpoints for tolerability and safety, with only mild AEs being related to EVX-01. R&D Day Highlights Preclinical Data on genetic adjuvant technology On May 25, Evaxion hosted a series of talks from its scientists and collaborators, sharing preclinical data on its proprietary genetic adjuvant technology developed to enhance the effectiveness of DNA and mRNA vaccines. The genetic adjuvant carries the code for CCL19, a molecule known to attract immune cells, notably antigen presenting cells, and can be encoded into either DNA or mRNA vaccines to boost the immune response. The technology boosts both B cell and T cell immune responses, making it applicable to a wide range of vaccines, both for cancer and for infectious disease. Next-generation cancer immunotherapy based on ERVs On March 23, Evaxion announced that it has developed a new proprietary AI platform technology, ObsERV™, identifying a new source of targets for personalized cancer therapy. ObsERV™ makes it possible to identify patient-specific virus targets, so-called ERVs (endogenous retroviruses), selectively expressed in cancer. Evaxion has demonstrated that ERVs are strongly associated with the overall survival of cancer patients, and notably of patients with cold tumors that are normally unresponsive to immunotherapy. Evaxion anticipates filing a clinical trial application (CTA) with the European Medicines Agency in Q3 2023 for its next-generation DNA-based cancer immunotherapy utilizing the OBsERV technology and intends to begin a Phase 1 trial in Q4 2023 in patients with solid tumors, subject to additional funding being obtained. First Quarter of 2023 Financial Results Cash position: As of March 31, 2023, cash and cash equivalents were $10.2 million as compared to $13.2 as of December 31, 2022. Operating spending for the first quarter of 2023 was offset by the proceeds from issue of shares and exercise of warrants. We expect that our existing cash and cash equivalents, will be sufficient to fund our operating expenses and capital expenditure requirements into early December 2023. Research and Development expenses were $3.9 million for the quarter ended March 31, 2023 as compared to $4.8 million for the quarter ended March 31, 2022. The decrease was primarily due to a decrease in external costs offset by an increase in employee-related costs as a result of higher headcount. General and Administrative expenses were $2.5 million for the quarter ended March 31, 2023 as compared to $1.6 million for the quarter ended March 31, 2022. The increase was primarily due to an increase in external costs for planning of equity financing. Net loss was $6.2 million for the quarter ended March 31, 2023 or ($0.24) per basic and diluted share as compared to a net loss of $5.8 million, or ($0.25) per basic and diluted share for the quarter ended March 31, 2022. About Evaxion Evaxion Biotech A/S is a clinical-stage, pioneering company, advancing AI-powered immunotherapies. Evaxion’s proprietary and scalable AI technologies decode the human immune system to discover and develop novel immunotherapies for cancer, bacterial diseases, and viral infections. Evaxion has a broad pipeline of candidates, including three clinical-stage, personalized cancer immunotherapies. The Company is located in Hørsholm, Denmark and listed on the Nasdaq New York stock exchange. For more information, please visit Source: Evaxion Biotech Forward-looking statement This announcement contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. The words “target,” “believe,” “expect,” “hope,” “aim,” “intend,” “may,” “might,” “anticipate,” “contemplate,” “continue,” “estimate,” “plan,” “potential,” “predict,” “project,” “will,” “can have,” “likely,” “should,” “would,” “could,” and other words and terms of similar meaning identify forward-looking statements. Actual results may differ materially from those indicated by such forward-looking statements as a result of various factors, including, but not limited to, risks related to: our financial condition and need for additional capital; our development work; cost and success of our product development activities and preclinical and clinical trials; commercializing any approved pharmaceutical product developed using our AI platform technology, including the rate and degree of market acceptance of our product candidates; our dependence on third parties including for conduct of clinical testing and product manufacture; our inability to enter into partnerships; government regulation; protection of our intellectual property rights; employee matters and managing growth; our ADSs and ordinary shares, the impact of international economic, political, legal, compliance, social and business factors, including inflation, and the effects on our business from the worldwide COVID-19 pandemic and the ongoing conflict in the region surrounding Ukraine and Russia; and other uncertainties affecting our business operations and financial condition. For a further discussion of these risks, please refer to the risk factors included in our most recent Annual Report on Form 20-F and other filings with the U.S. Securities and Exchange Commission (SEC), which are available at . We do not assume any obligation to update any forward-looking statements except as required by law. Evaxion Biotech A/S Consolidated Statements of Financial Position Data (Unaudited) (USD in thousands) Mar 31, 2023 Dec 31, 2022 Cash and cash equivalents $10,240 $13,184 Total assets 20,488 22,025 Total liabilities 13,913 13,722 Share capital 4,217 3,886 Other reserves 81,080 77,076 Accumulated deficit (78,722) (72,659) Total equity 6,575 8,303 Total liabilities and equity 20,488 22,025 Evaxion Biotech A/S Consolidated Statements of Comprehensive Loss Data (Unaudited) (USD in thousands, except per share data) Three months Ended Mar 31, 2023 2022 Research and development expenses $3,852 $4,804 General and administrative expenses 2,542 1,595 Operation loss (6,394) (6,399) Finance income 285 519 Finance expenses (326) (158) Net loss before tax (6,435) (6,038) Income tax benefit 194 247 Not loss for the period $(6,241) $(5,791) Net loss attributable to equity holders of Evaxion Biotech A/S $(6,241) $(5,791) Loss per share - basic and diluted $(0.24) $(0.25) Number of shares used for calculation (basic and diluted) 25,783,847 23,203,808 As mentioned 31. December 2022 the financial statement had been prepared using the going concern assumption. Based on the Company’s current cash position, with a cash runway until early December 2023, there is a need for further funding, to mitigate the Company’s ability to continue as a going concern. For more information Evaxion Biotech A/S Per Norlén Chief Executive Officer pno@evaxion-biotech.com +45 53 53 49