Mirror Biologics, Inc.

From all of us at Mirror Biologics, we want to wish you an enjoyable Memorial Day celebrated with friends and family. As we celebrate, may we remember and never forget those who served and those that made the ultimate sacrifice for our freedom so that we all might be considered hero’s. “A hero is someone who understands the responsibility that comes with his freedom.” — Bob Dylan This quote also underscores the importance of remembering and honoring all those affected by conflict and violence. In this context, we also remember in our prayers the horrifying tragedy that unfolded on October 7, 2023. In this devastating event, Hamas terrorists rampaged through southern Israeli communities, perpetrating unspeakable acts of violence against innocent civilians. On this day where over 1200 people lost their lives, there were also remarkable stories of heroism that emerged amidst the chaos and tragedy on this day. As we remember all the sacrifices of all heroes that fight and sacrifice for freedom, Mirror also wishes to remind us that: “Life is like a mirror; we get the best results when we smile at it.” - Unknown. Happy Memorial Day!

We are very pleased to welcome Oscar Segurado, MD, PhD to the growing Mirror Biologics team as our Chief Medical Officer. Dr Segurado is an industry veteran with over 30 years experience in global biopharmaceutical development with extensive clinical expertise in immuno-oncology, including previous senior positions at Abbott, AbbVie (HUMIRA), Becton Dickinson, Myrad Genetics/Crescendo Bioscience and ASC Therapeutics. As both an MD and a PhD immunologist, he also has over 10 years of academic work experience as a tenured Professor of Immunology and over 100 peer-reviewed publications. Dr Segurado will be leading our efforts to advance our metastatic colorectal cancer clinical development efforts to a Phase II/III registration trial. Please join us in giving Dr Segurado a warm welcome!

New hope for metastatic cancer patients! Metastatic colorectal cancer tumors are cold tumors that do not respond to checkpoint blockade immunotherapy. AlloStim converts cold tumors to hot. Here we report a rare objective response to checkpoint blockade after priming with AlloStim. A Phase IIB study is now being planned to expand the study of this combination.

MIRROR REFLECTION: The Art of War on Disease Imagine the human body as a vast kingdom, and within it, the immune system acts as the kingdom’s defense force. Just like in a war, the immune system’s primary goal is to protect the kingdom (body) from invaders (pathogens). Immunotherapy is the science that attempts to harness the power of the immune system to either protect or combat against disease. Protection involves education and memory. However, disease by definition is a failure of the immune system to protect. In existing disease situations, it is not enough to boost the immune soldiers of war, as these are the same soldiers which allowed the disease in the first place. It is necessary to first educate the troops before sending them to battle. Sun Tzu’s “The Art of War” it is taught: "Victorious warriors win first and then go to war, while defeated warriors go to war first and then seek to win." To develop the next generation immunotherapies being pioneered at Mirror Biologics, we first educate the immune soldiers before we send them into war against disease. The education does not require any gene editing. Developing the next generation of educated immune warriors is our in-house team of immunologists, physicians, molecular biologists, engineers and cell culture specialists. We call this amazing team of Superhero’s the CELLVENGERS. We are growing and seeking talent. Do you have what it takes to be a CELLVENGER super hero? We are making a difference in the lives of many suffering from such evil diseases as metastatic cancer and viral pneumonia.

MIRROR REFLECTION: Immune Compound Interest What if you could earn compound interest on your cellular immune function? Instead of losing function over time as you age, imagine the function growing over time like an investment earning compound interest. This is the novel design of our AlloPrime immunomodulatory vaccine. Albert Einstein once said: "Compound interest is the eighth wonder of the world. He who understands it, earns it… he who doesn’t… pays it." Compound interest refers to the interest earned not only on the initial principal amount but also on the accumulated interest from previous periods. The more frequently interest is compounded, the faster your money grows. Cellular immune function grows from birth upon each new exposure to environmental pathogens. Each exposure is influenced by a previous exposure. Thus over time a robust pool of memory cells is formed that can respond to pathogen encounters both specifically or through a by-stander effect. However, this accumulated immune memory declines as we age in a process known as “immunosenescence”. By combining the concepts of heterologous immunity and the hygiene hypothesis, Mirror Biologics has developed an immunomodulatory vaccine called “AlloPrime” to convert the aging immune system into a young immune system ready to learn. AlloPrime does not incorporate any viral antigens. Instead it remodels the cellular immune system to restore Th1 cellular immune function. The effect is most dramatic in the elderly senescent immune system. A novel result of this remodeling of the elderly immune system is that the cellular immune function can increases over time upon each encounter with an environmental pathogen. AlloPrime thus can provide universal viral protection to the elderly against known viruses such as Influenza, RSV and coronavirus, as well as unknown future viruses with pandemic potential with this self-amplifying immune mechanism. The novel self-amplifying increases in cellular immune function over time, works just like compound interest. A payment of increased cellular immunity is made upon each viral encounter. The more encounters, the richer the cellular immune function. This mechanism may eliminate the need for annual flu vaccines and booster injections. We hope to provide seniors that invest in 5 AlloPrime intradermal injections over 14 days, to become rich with a life time of healthy aging compounded interest! AlloPrime has completed a Phase I/II clinical trial in 40 healthy adults over 65yo. Subjects were followed over one year to monitor changes in their cellular immune function over time and the ability of their immune cells to suppress viral lytic activity of influenza A, influenza B, RSV and coronavirus in an ex-vivo assay, even though no viral antigens were incorporated in the vaccine formulation. Data is now being analyzed and prepared for peer review and publication. #vaccine

MIRROR REFLECTION: PASSOVER We wish all our employees, friends and collaborators that celebrate a Happy Passover. Passover, or Pesach, celebrates the themes of redemption and freedom. On this occasion we pray for freedom for all hostages and innocents held against their will. On this occasion, we also recognize those that struggle against diseases, such as cancer, and the hope for deliverance and freedom from suffering through the combined efforts of the research and medical communities. Passover occurs in the spring, a time of rebirth and renewal. This can be paralleled with our efforts to rejuvenate the immune systems of seniors in order that new, healthy immune cells might replace those that have become senescent. The hope for a “renewed” body free of cancer and with renewed immune competence echoes the Passover theme of starting anew. By integrating the themes of liberation from cancer and disease and the rejuvenation of the immune system in senior adults into the Passover narrative, we at Mirror Biologics celebrate the ongoing quest for healing and renewal in our lives. 🌿🍷 חג פסח שמח

We welcome Elizabeth Czerepak to our team! Elizabeth will join us as Chief Financial Officer (CFO) and Vice President of Corporate Development. Elizabeth has served as CFO of several public and private biotechs over the last 13 years, including revenue-stage companies, leading IPOs for several of them. She also has 10 years of venture capital investment experience as a former Managing Director at Bear Stearns and JPMorgan, and Founding General Partner of Bear Stearns Health Innoventures L.P. Elizabeth also has 18 years experience in big pharma serving in senior leadership positions managing finance, strategic planning, business development and commercial launch teams. Notably, Elizabeth led the global search to partner D2E7 (Humira®), which culminated in BASF Pharma’s sale to Abbott for $6.9 billion. Elizabeth also played a key role in Roche’s acquisition of Syntex for $5.4 billion. Elizabeth’s experience as a CFO leading private and public financings and navigating complex financial transactions and her reputation for managing biotechnology investments in a manner that have created value for investors are key skills which we believe will contribute significantly to our efforts to build the necessary infrastructure to advance our programs to late stage clinical development and eventual commercialization.

MIRROR REFLECTION: IS THE FOUNTAIN OF YOUTH IN TAMPA? Over the centuries many explorers have sought after the elusive Fountain of Youth as a remedy for aging. In the 16th century the legend became prominent when Juan Ponce de León was searching for the Fountain of Youth in Florida. He may have been in the right place, but just a few centuries too early! Is it possible that the Fountain of Youth can be found today in Tampa, Florida? Mirror Biologics, headquartered in Tampa, has developed a technology designed to convert an old senescent immune system into a youthful immune system. Such a conversion is like a Fountain of Youth, potentially reversing the effects that lead to diseases of aging, such as viral community acquired pneumonia (CAP). CAP is common in adults and is a leading cause of morbidity and mortality worldwide. About 100 million cases of CAP occur in adults every year. The economic burden of CAP in the USA alone has been estimated to be >$17 billion. According Our World in Data, the number of deaths among those aged 70 and older due to pneumonia increased from around 600,000 in 1990 to over 1 million in 2019. This rise is attributed largely to the growing and aging global population. The death rate from pneumonia is highest in sub-Saharan Africa and South East Asia. Respiratory viral infection in younger adults results in mild to moderate upper respiratory tract illness characterized by fever and productive cough and low mortality, while senior adults, particularly those with co-morbidities, experience a high incidence of severe pneumonia, often characterized by respiratory distress, sepsis and high rate of mortality. Cellular immunity is vital for identifying and eliminating virus-infected cells, preventing viral replication, and establishing long-term protection against future infections. Age-related dysfunction of cellular immunity contributes to the vulnerability of elderly individuals to viral infection, including progressive declines in both innate and adaptive cellular immune function. AlloPrime is designed to restore cellular immune function in the elderly, converting an aged immune system into a youthful immune system. This conversion is predicted to provide the elderly with universal viral protection, both from known viruses (e.g., influenza, RSV and corona virus) and future unknown viruses or new mutated strains of existing viruses. A Phase I/II clinical study of AlloPrime in 40 adults over 65yo has been completed which evaluated longitudinal blood samples after AlloPrime vaccination at 30 days, 6 months and 1 year. Data on restoration of cellular immunity and protection from multiple viruses is being analyzed and the results being prepared for publication. Promising preliminary data indicates that Juan Ponce de León may have been searching in the right place for the Fountain of Youth, just a few centuries too early. The Fountain of Youth may actually be resident in Tampa!

MIRROR REFLECTION: The Secret Sauce At Mirror Biologics we are often asked: “How can AlloStim®, a non-genetically manipulated, living immune cell therapy for solid tumors, be off-the-shelf and not cause GVHD and at the same time be personalized for a patient’s own tumor without need for prior knowledge of the tumor type or knowledge of patient-specific neoantigens, phenotypical identity or genetic mutational status of the resident tumor. What is the “secret sauce”? 🤔 To some, these claims sound like they were cooked up like a witches brew conjering up the scene from the Shakespearean play Macbeth where the witches stir their mystical cauldron with the famous chant: “Double, double, toil and trouble, Fire burn and cauldron bubble. Fillet of a fenny snake, In the cauldron boil and bake; Eye of newt and toe of frog, Wool of bat and tongue of dog, Adder's fork and blind-worm's sting, Lizard's leg and owlet's wing, For a charm of powerful trouble, Like a hell-broth boil and bubble. Double, double, toil and trouble, Fire burn and cauldron bubble.” Macbeth Act 4, Scene 1 The fact is that the AlloStim® protocols are designed to recreate a cascade of immunological actions based upon well-established scientific principals that can be reflected or “mirrored” upon a host both temporally and spatially to create a novel outcome. Here are the key ingredients of the special sauce: 1. Intradermal injection. The injection of fully mismatched AlloStim® under the skin rich in antigen-presenting Langerhans cells results in the creation of anti-alloantigen type 1 immunity, increasing the Th1/Th2 titer. 2. Intravenous Infusion: The rejection of AlloStim® in the circulation in an allo-primed patient causes the release of type 1 cytokines which non-specifically activate the Th1 memory cells and NK cells by by-stander effects. These activated immune cells naturally extravasate and migrate to sites of inflammation, including tumor lesions changing the tumors from ‘cold’ to ‘hot’. 3. In-situ Vaccination: The presence of activated NK cells in the tumor microenvironment elicits immunological cell death, releasing danger signals and chaperoned tumor neoantigens into the tumor microenvironment conditioned with release of inflammatory from the infiltrating Th1 cells. This enables the processing of tumor neoantigens by local dendritic cells which mature and migrate to lymph nodes priming for tumor-specific adaptive immunity. In this manner an off-the-shelf cell therapy creates patient-specific adaptive immune response to a resident tumor. It is not magic but it is an immunological trick. So as the witches say: "Fair is foul and foul is fair: Hover through the fog and filthy air." We hope this helps clear the fog on the AlloStim® secret sauce.

We wish our employees, colleagues, shareholders, followers and friends a happy Easter! May this day be filled with joy, renewal, hope and imagination. As we push the reset button for new beginnings, let’s imagine a future without cancer. Albert Einstein once said: “Imagination is everything. It is the preview of life’s coming attractions.”