INmune Bio (NASDAQ: INMB) Confirms Belief That They Are The First To Successfully Generate mlNK cells In Patients

The innate immune system is one of two basic arms of the human immune system; the other being the adaptive arm. Like adaptive immunity, the innate immune system consists of a variety of cells and soluble factors and the principal cytotoxic cell is the natural killer (NK cell). These cells are essential for survival and, in addition to directly killing infected cells and cancer cells, NK cells facilitate cross-talk between the innate and adaptive immune system by interacting with dendritic cells and secretion of immunostimulatory cytokines. Both the innate and adaptive immune system are important in controlling cancer; however, the interplay between the two is very complicated and not completely understood.

NK cells of the innate immune system have two primary functions: to kill virally infected cells and to kill cancer cells.  We focus on their role in killing cancer cells.  NK cells play an important role in preventing cancer.  That is, every day our bodies make precancerous cells.  Our circulating immune system seeks these abnormal cells.  When an NK cell contacts a precancerous cell, it kills it.  This process, called Immune Surveillance, keeps us cancer free.   An NK cell must come in direct contact with the cancer cell and bind tightly in order to kill it.  The NK cells kill target cells by two mechanisms, first by secretion of perforin molecules which create holes in the cancer cell membrane and allow entry of NK-cell secreted enzymes called “granzymes” into the cancer cell, which kills the cell. This is called “NK cell degranulation”.  The second killing mechanism is by binding to “death receptor” molecules on the surface of the cancer cells and signalling to the cell to commit suicide by a process called “apoptosis”. Cancers arise because the immune response fails to detect them, or the cancer cells are resistant to killing or, simply because the cancer cells grow more quickly than the immune response can deal with them. Chemotherapy and radiotherapy reduce the tumor burden but it is unlikely that either is curative alone; we probably need an immune response to eradicate the disease.

NK cells need multiple activating signals to progress from a resting state to the triggering of cytolysis and cytokine secretion. INmune Bio has studied these pathways extensively and demonstrated that binding of NK cells with INKmune™ provides multiple activating signals and drives resting NK to the phenotype of memory-like NK (mlNK) cells with enhanced cancer-killing function.

Immune Bio’s INKmune^TM is a pharmaceutical-grade, replication-incompetent human tumor cell line which conjugates to resting NK cells and delivers multiple, essential priming signals akin to treatment with at least three cytokines in combination. INKmune™ is stable at -80^oC and is delivered by a simple IV infusion. The INKmune:NK interaction ligates multiple activating and co-stimulatory molecules on the NK cell and enhances its avidity of binding to tumor cells; notably those resistant to normal NK-mediated lysis. Tumor-primed NK (TpNK) cells can lyse a wide variety of NK-resistant tumors including leukemias, lymphomas, myeloma, ovarian cancer, breast cancer.

After the markets closed on Wednesday, August 25th, Boca Raton, FL based VP Watchlist company INmune Bio, Inc. (NASDAQ: INMB), a clinical-stage immunology company focused on developing treatments that harness the patient’s innate immune system to fight disease, announced that the first patient who received INKmune™ as a potential treatment for high-risk myelodysplastic syndrome (MDS) has successfully shown the NK activation and functional differentiation predicted by previously published in vitro experiments. The company believes that this is the first ever successful generation of mlNK cells in patients. Preliminary data from the first patient shows that formation of mlNK cells can be achieved in vivo and without toxicity. INKmune™ was delivered in three doses on days one, eight and 15. INKmune™ therapy cause proliferation of NK cells with a doubling of the number of peripheral blood NK cell numbers on day 8. Over 50% of the expanded NK cells had an activated profile (CD69+/CD25+) on days eight and 15 and increased to over 70% by day 29. More than 80% of the activated NK cells expressed markers associated with a memory-like NK cell (CD57++, NKG2D+, NKG2A-ve, NKp46-ve). In vitro, the INKmune™ activated NK cells were better at killing cancer cells than the patient’s own NK cells prior to treatment, with an 82% increase in lysis of K562 leukemia cells and a 47% increase in lysis of NK-resistant RAJI lymphoma cell tumor cells as early as day eight. Despite this high level of activated NK cells and tumor killing, the patient showed no symptoms of Cytokine Release Syndrome (CRS). At least nine additional patients with high-risk MDS will be enrolled in the ongoing Phase I trial.   A video overview of the INKmune™ platform can be found by clicking here.

 

Dr. Mark Lowdell PhD, chief scientific officer of INmune Bio (NASDAQ: INMB)

“The INmune Bio team has been developing the concept of tumor cell-primed NK cells since 2004 with the creation of the first pharmaceutical-grade tumor line for NK priming a critical first step in testing whether these primed, memory-like NK cells could be generated in vivo. In the lab, INKmune™ binds to multiple NK ligands and initiates the activation of over 3,000 genes associated with function, trafficking, proliferation, and survival to form memory-like NK cells, which have superior cancer killing function. In our hands, no single cytokine has such broad physiological effects on NK cells compared to INKmune-primed NK cells, and this has inspired us to refer to INKmune™ as a pseudokine. We are always cautious of single patient data but seeing these significant changes in peripheral blood NK cell populations in a patient treated at the lowest dose of INKmune™ is encouraging and identical to what we observed in pre-clinical studies” stated Dr. Mark Lowdell PhD, chief scientific officer of INmune Bio (NASDAQ: INMB).

 

RJ Tesi, M.D., chief executive officer of INmune Bio (NASDAQ: INMB)

“Data from this patient demonstrates that INKmune™ can produce memory-like NK cells in patients. These biomarker data demonstrate that, even in a heavily pre-treated patient, INKmune™ can cause proliferation of the patients NK cells and convert them into the type of NK cells that are superior at killing cancer cells,” stated RJ Tesi, M.D., chief executive officer of INmune Bio (NASDAQ: INMB).

About INmune Bio, Inc.:

INmune Bio, Inc. is a publicly traded (NASDAQ: INMB), clinical-stage biotechnology company focused on developing treatments that target the innate immune system to fight disease. INmune Bio has two product platforms. The DN-TNF product platform utilizes dominant-negative technology to selectively neutralize soluble TNF, a key driver of innate immune dysfunction and mechanistic target of many diseases. DN-TNF is currently being developed for COVID-19 complications (Quellor™), cancer (INB03™), Alzheimer’s and Treatment Resistant Depression (XPro1595), and NASH (LIVNate™). The Natural Killer Cell Priming Platform includes INKmune™ aimed at priming the patient’s NK cells to eliminate minimal residual disease in patients with cancer. INmune Bio’s product platforms utilize a precision medicine approach for the treatment of a wide variety of hematologic malignancies, solid tumors and chronic inflammation with components of the innate immune system. To learn more, please visit www.inmunebio.com. Here’s a link to INMB’s presentation.

David Moss, CFO INmuneBio (INMB)

“With the completion of a registered direct offering during July 2021 in which the Company raised $36.9 million of net proceeds combined with the Company raising $15.0 million of net proceeds from the sale of common stock through the ATM, also in July 2021, we are well financed to Phase 2 Alzheimer’s data and other milestones such as clinical data from INKmune and other developments with our DN-TNF franchise assuming no material delays caused by the pandemic,” said David Moss, CFO INmuneBio (INMB).

Financial Results for the Second Quarter Ended June 30, 2021:

• Net loss attributable to common stockholders for the quarter ended June 30, 2021 was approximately $6.7 million, compared to approximately $2.1 million for the quarter ended June 30, 2020.
• Research and development expense totaled approximately $4.5 million for the quarter ended June 30, 2021, compared to approximately $0.9 million during the quarter ended June 30, 2020.
• General and administrative expense was approximately $2.1 million for the quarter ended June 30, 2021, compared to approximately $1.2 million during the quarter ended June 30, 2020.
• As of June 30, 2021, the Company had cash and cash equivalents of approximately $39.5 million.
• As of August 4, 2021, the Company had approximately 17.7 million common shares outstanding.

Upcoming Milestones:

• Report on Phase 1b data for XPRO™ Alzheimer’s disease trial.
• Initiate XPRO™ Phase 2 program for Alzheimer’s disease in patients with neuro-inflammation by year-end 2021.
• Initiate XPRO™ Phase 2 program for treatment resistant depression, funded in part by a $2.9 million NIH grant, by year-end 2021.
• Report on first group of patients treated with Quellor™ as part of Phase 2 trial in patients with COVID 19 infection and respiratory compromise.
• Report on biomarkers from the INKmune™ high-risk MDS Phase 1 trial before year end.