Pattern Pharma

Making Patients Innately Better

Pattern Pharma is a biopharmaceutical company with therapeutics that mobilize innate immunity to address the immune failures underpinning many diseases, with a particular focus on cancer. The innate immune system is the frontline against all infectious agents as well as emerging cancers and is also the crucial gateway to the adaptive immune system – it is thus a crucial bedrock of human health that has been largely unexploited to date. In oncology in particular, most immunotherapeutics exploit the adaptive immune system and have had relatively little success against solid tumors (which make up 90% of all cancers).

Pattern’s scientific cofounders showed that innate immune cells are activated by receptor clustering and discovered a patent-protected compound (PPI-100) which did this safely.

Pattern’s focus is on deploying PPI-100 in the perioperative setting to address the 40% relapse rate in cancer patients 5 years after surgical resection.

Toll-Like Receptors

The innate immune system senses threats through hard-wired receptors (Pattern Recognition Receptors) which include Toll-Like Receptors (TLRs). TLRs are usually expressed in innate immune cells such as macrophages and dendritic cells (DCs), and are found on cell membranes or intracellular vesicles. TLR4 was the first TLR identified in humans (1997) and is the most studied member of the TLR family; it further has unique properties as compared to other TLRs, including that it alone utilizes two independent signaling pathways (MyD88-dependent and TRIF-dependent) to activate a broad immune response.

Despite extensive efforts over the past decades, there have been no FDA-approved TLR4 therapeutics to date. Pattern has, though, solved the long-standing challenge of safely and effectively drugging this previously undruggable target. In more detail, Pattern’s scientific co-founders discovered a key mechanism (receptor clustering) by which innate immune cells can be safely and efficaciously activated and, based on this understanding, launched a program that resulted in Pattern’s patented lead asset, PPI-100. In the course of this program, they generated substantial amounts of supporting human clinical data which significantly de-risk PPI-100.

PPI-100: Our Lead Product

PPI-100 is a TLR agonist that activates DCs and macrophages, by agonizing four of the five Toll-like receptors (TLRs) found on the cell membranes of innate immune cells, predominantly TLR4 but also TLR1, TLR2 and TLR6. This causes the activated cells to become killer DCs and killer macrophages, which in turn activates NK cells. PPI-100 also increases antigen-presenting activities of DCs and macrophages directed towards tumor antigens, which results in anti-cancer cytotoxic T-cells, antibodies and long-term T-cell memory.

Pattern has generated extensive amounts of data (including in the 4T1 murine cancer model) that indicate that PPI-100 is able to invoke a powerful anti-tumor immune program, key aspects of which program are:

Blood monocytes are activated, reprogrammed into an anti-cancer state and leave the bloodstream where they serve as anti-tumor tissue macrophages in tumor tissues

Having been reprogrammed into an anti-cancer cytotoxic state, stimulated DCs and macrophages secrete a range of immunostimulatory cytokines

Stimulated DCs in turn stimulate (via secretory IL-12 ) the anti-tumor cytotoxic capacity of NK cells

Stimulated DCs are also highly effective at antigen processing of cancer cells and presenting them to T cells, in part since they express co-stimulatory receptors (CD86, CD80, CD40) and MHC Class 1 and Class 2 molecules necessary for the initiation of the antigen-recognizing T-cell responses

A strong anti-tumor response from CD4 T cells and CD8 T cells is induced, leading to the production of IFN-γ by CD8 T cells

Long-term anti-cancer T-cell memory is induced to guard against relapses

The result is a broad immune response which then returns to baseline as standard immune dampening mechanisms kick in.

In summary, PPI-100 is an “off-the-shelf” therapeutic which is able to induce a personalized immune response against a given individual’s cancer.

PPI in the Perioperative Setting

Response rates to cancer immunotherapy remain unsatisfactorily low. Current approaches deliver these therapies to patients with advanced disease and a preferable approach might be to deliver immunotherapy in the context of a minuscule tumor burden to be found post-surgery. In this context, PPI-100 can help generate systemic immunity by reprogramming the body’s response to surgery from an immunosuppressive to an immunoactive one, leading to the eradication of residual disease in the postoperative bed of the resected tumor and in metastases in different body tissues such as lymph nodes, spleen, lungs, liver, etc.

Pattern is hence focused on the development of PPI-100 for the perioperative treatment of cancer patients undergoing surgical resection for whom rapid tumor recurrence is of significant clinical concern, noting that surgery is the standard of care for most patients with solid tumors but more than 40% of patients suffer a relapse within five years. Broadly, our approach engages both the innate & adaptive machinery of the immune system to prevent both local tumor recurrence and to mitigate the risk of the formation of distant metastases.

PPI-100 achieves these results by virtue of its impact on myeloid lineage cells (dendritic cells, monocytes, and macrophages) and, through these cells, on innate lymphoid cells such as NK cells. Noteworthy in this regard is that a large proportion of immune cells in & around solid tumors, in the tumor microenvironment, derive from the innate immune system being mainly myeloid lineage cells and innate lymphoid cells – which constitute prime targets for activation by PPI-100.

Clinically, Pattern believes its approach has the potential to be broadly applicable across a wide spectrum of solid cancers that are resected, and its vision is thus that all cancer patients undergoing surgical tumor resection receive intraoperative immunotherapy to prevent post-surgical recurrence and metastasis.

More generally, based on its mechanism of action, PPI-100 may find application in a range of cancers, both as a monotherapy and in combination therapy. Additionally, based on data generated, PPI-100 has other applications against infectious diseases, or as a vaccine carrier/adjuvant.

Collaborations

Pattern collaborates with the MD Anderson Cancer Center, Massachusetts General Hospital (Harvard), the National Research Council of Canada (NRC), McGill University’s Goodman Cancer Institute, as well as the University of Toronto-affiliated Mount Sinai Hospital Research Institute and Princess Margaret Cancer Center.