Business description of RAPT-Therapeutics-Inc from last 10-k form

Overview

We are a clinical-stage immunology-based biopharmaceutical company focused on discovering, developing and commercializing oral small molecule therapies for patients with significant unmet needs in oncology and inflammatory diseases. Utilizing our proprietary drug discovery and development engine, we are developing highly selective small molecules designed to modulate the critical immune responses underlying these diseases. We have discovered and advanced into clinical development two unique drug candidates each targeting C-C motif chemokine receptor 4 (“CCR4”): FLX475 for the treatment of a range of tumors, and RPT193 for the treatment of allergic inflammatory diseases. We are also pursuing a range of targets, including general control nonderepressible 2 (“GCN2”) and hematopoietic progenitor kinase 1 (“HPK1”), that are in the discovery stage of development.

Through our team’s deep expertise in immunology and drug discovery, supported by advanced computational biology, we are developing the ability to exploit difficult targets, including through proprietary know-how. This proprietary drug discovery and development engine is built upon four key pillars: (i) computationally-driven disease target and biomarker identification; (ii) efficient design of small molecule drug properties; (iii) data-driven patient selection; and (iv) nimble clinical execution. We have leveraged this engine to identify and target CCR4, a key driver of the immune response in both oncology and allergic inflammatory disease.

Our lead oncology drug candidate, FLX475, is designed to selectively inhibit the migration of immunosuppressive regulatory T cells (“T_reg”) into tumors. We are currently in the Phase 2 portion of a seamless Phase 1/2 clinical trial to evaluate FLX475 as a monotherapy and in combination with pembrolizumab (marketed as Keytruda^®) in patients with several types of “charged” tumors and we anticipate results from the Phase 2 portion of the trial could provide clinical proof-of-concept (“PoC”). While we originally intended to provide an initial data readout from the Phase 1/2 trial in the second quarter of 2020, we now expect that timeline will be delayed due to circumstances and uncertainties created by the COVID-19 global pandemic.

Our lead inflammation drug candidate, RPT193, is designed to selectively inhibit the migration of type 2 T helper cells (“Th2 cells”) into allergically-inflamed tissues. Th2 cells are clinically validated drivers of allergic diseases along the “atopic march” such as atopic dermatitis (“AD”), asthma, chronic urticaria (skin rash), allergic conjunctivitis, chronic rhinosinusitis and eosinophilic esophagitis (inflammation of the esophagus). We believe that RPT193, if approved by the FDA, could fill an unmet medical need for the treatment of allergic disorders with the convenience of once-daily oral dosing. Due to circumstances and uncertainties created by the COVID-19 global pandemic, we have temporarily paused enrollment in the Phase 1b portion of our seamless Phase 1 trial of RPT193 in patients with AD. We will continue to monitor the situation and intend to restart enrollment in the clinical trial once circumstances related to the pandemic clarify.

We hold worldwide rights to each of our drug candidates, with the exception of the exclusive license granted to Hanmi Pharmaceutical LTD (“Hanmi”) for FLX475 in the Republic of Korea, the Republic of China (Taiwan) and the People’s Republic of China, including the special administrative regions of Macau and Hong Kong (the “Hanmi Territory”).

In November 2019, we completed our initial public offering (“IPO”), pursuant to which we issued an aggregate of 3,427,360 shares of our common stock at an offering price of $12.00 per share. Immediately prior to the closing of our IPO, all outstanding shares of our convertible preferred stock converted into 17,467,184 shares of our common stock. In aggregate, the shares issued in our IPO generated approximately $33.8 million in net proceeds after deducting underwriting discounts and other offering related costs.

We incorporated in March 2015 in the State of Delaware under the name FLX Bio, Inc. and changed our name to RAPT Therapeutics, Inc. in May 2019. Our corporate headquarters are in South San Francisco, California.

Diversified Pipeline

Our Strategy

Our CCR4 Franchise

Our proprietary drug discovery and development engine has identified the cell-surface receptor CCR4 as a drug target that potentially has broad applicability in oncology and inflammatory diseases. T cells, a type of white blood cell, play crucial roles in immunological memory, regulation and responses. Two T cells of clinical interest are T_reg and Th2 cells, both of which express CCR4, a cell-surface receptor that binds to chemokines that orchestrate cell migration and homing throughout the body. The two chemokines that bind to this CCR4 receptor, C-C motif chemokine ligand 17 (“CCL17”) and C-C motif chemokine ligand 22 (“CCL22”), are over expressed and secreted by tumors and allergically inflamed tissues. This over expression allows for the theoretical manipulation of CCR4 and its two T cell subtypes to address diseases across the immunological continuum spanning underactive to overactive immune responses in oncology and allergic inflammatory disease.

In cancer, CCR4 chemokines recruit immunosuppressive T_reg to tumor sites. T_reg represent a dominant pathway for downregulating the immune response, and thus may limit the effectiveness of currently available therapies such as checkpoint inhibitors. CCR4 is highly expressed on T_reg and not highly expressed or used by effector or cytotoxic T cells, suggesting that targeting CCR4 may selectively block T_reg migration into tumors. We believe that a therapeutic drug that specifically inhibits T_reg migration into tumors has the potential to bring therapeutic benefit to patients across a wide spectrum of tumors in a manner similar to other immuno-oncology therapies that have been shown to be effective against multiple tumor types, while also potentially deepening or broadening clinical responses to these therapies, all without the serious risks associated with current CCR4 approaches that systemically deplete T cells and broadly suppress the immune system.

In allergic inflammatory diseases such as AD and asthma, CCR4 chemokines recruit Th2 cells to inflamed tissues. Once these Th2 cells enter certain tissues, such as the skin or the airways in the lung, they secrete products known to drive the inflammatory response. In allergic asthma, Th2 cells have been shown to play a pivotal role in airway inflammatory response and airway remodeling, and CCR4 is essential in recruiting Th2 cells to asthmatic airways. Similarly, murine models and ex vivo studies strongly suggest that CCR4 plays a critical role in allergic inflammation in AD as blocking the migration of Th2 cells has been shown to reduce allergic inflammation in the skin and the lung. We believe that CCR4 antagonists have the potential to suppress allergic inflammation in patients in a clinically meaningful manner.

CCR4 Drives Tumor Progression and Allergic Inflammation

Our Lead Oncology Drug Candidate—FLX475

Our lead oncology drug candidate, FLX475, is an oral small molecule CCR4 antagonist that is designed to selectively inhibit the migration of immunosuppressive T_reg into tumors while sparing T_reg in healthy tissues and without negatively impacting effector immune cells, which we believe may decrease the likelihood of side effects.

We own an issued U.S. composition of matter patent directed to FLX475 that is scheduled to expire in 2037 (not including any applicable extensions, if approved). We have entered into a collaboration and license agreement with Hanmi, whereby we granted Hanmi the exclusive rights to develop, manufacture and commercialize FLX475 in the Hanmi Territory.

FLX475: Highly Selective Approach for Targeting Tumor T_reg

We are developing FLX475 for the treatment of a broad range of “charged” tumors, which represent cancer types we believe are most likely to respond to FLX475. Our proprietary drug discovery and development engine has identified certain tumors in which the abundance of T_reg is likely to be a cause of immune suppression. We refer to these tumors as “charged,” as defined by their expression of high levels of (i) CCR4 ligands, (ii) T_reg and (iii) CD8+ effector cells. Tumors with high levels of these three parameters imply they have the necessary components to generate a potent immune response; however, the presence of T_reg dampens this response. We have identified numerous tumors as being charged, including non-small cell lung cancer (“NSCLC”), triple negative breast cancer (“TNBC”), head and neck squamous cell carcinoma (“HNSCC”), nasopharyngeal cancer (“NPC”), gastric cancer, certain Hodgkin (“HL”) and non-Hodgkin lymphomas (“NHL”), and cervical cancer. The data presented in the diagram below was derived from an in-house analysis of The Cancer Genome Atlas Database and additional published sources and confirmed by us through in situ hybridization of over 400 tumor microarray samples.

Identification and Characterization of “Charged” Tumors

The graph above reflects a logarithmic scale on each axis.

Additionally, we have discovered that the presence of oncogenic viruses, such as Epstein-Barr virus (“EBV”) (as shown in the diagram below) and human papillomavirus (“HPV”), is associated with tumors that are highly “charged” and can be prospectively selected. In preclinical studies, we have demonstrated an association between EBV and CCR4 ligand expression, which is believed to be causal to T_reg migration. These studies are further validated by scientific publications linking EBV to T_reg tumor infiltration in HL, gastric cancer and NPC.

“Charged” Tumors Include EBV-Associated Tumors

EBER1 = EBV-encoded RNA1

Oncology Market Overview

Significant progress in cancer treatment has been made recently with the development of highly targeted and immuno-oncology-based therapies. Remarkable clinical response rates have been observed with targeted therapies in selective patient populations, while in a subset of a broad range of tumors, immuno-oncology products have demonstrated durable responses and possible cures. Although true breakthroughs have been achieved, often only a very narrow segment of the patient population can be treated or are responsive to these novel therapies. Hence, there remains a significant unmet medical need for a majority of tumor types including “charged” tumors in which we intend to develop FLX475 either as a monotherapy or in combination with immune checkpoint inhibitors such as pembrolizumab or other agents.

A Large Proportion of Multiple Tumor Types are “Charged”

Non-Small Cell Lung Cancer

NSCLC is the most common type of lung cancer, representing 84% of all lung cancer cases in the United States. Squamous cell carcinoma (“NSCLC Sq.”), adenocarcinoma (“NSCLC Ad.”) and large cell carcinoma are all subtypes of NSCLC. Lung cancer is the leading cause of cancer death for both men and women. In 2019, an estimated 142,670 people in the United States will die from lung cancer. There are approximately 228,000 diagnoses of lung cancer annually in the United States. Despite the availability of numerous therapies, the prognosis remains poor, with an overall five-year survival rate for all patients diagnosed with NSCLC as low as 19.4%.

Standard therapies include surgery, chemotherapy and radiation therapy. Up to a third of NSCLC patients have tumors with mutations in genes (such as epidermal growth factor receptor and anaplastic lymphoma kinase) for which molecularly-targeted therapies have been approved (such as erlotinib, gefitinib or crizotinib). However, these treatments usually do not result in long-term remissions, and the tumors generally return and become resistant to therapy.

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Immunotherapies that target PD-1 or the PD-1 ligand (“PD-L1”) (e.g. pembrolizumab, nivolumab and atezolizumab) have recently been approved for the treatment of patients with advanced or metastatic NSCLC either alone (for previously untreated or treated patients), or in combination with chemotherapy (for previously untreated patients). While treatment with these immunotherapy agents in NSCLC has resulted in promising activity ranging from approximately 15-30% overall response rates in previously treated patients to approximately 40-60% response rates in combination with chemotherapy in previously untreated patients. However, approximately 50-80% of patients do not respond to these therapies, indicating significant unmet medical need remains.

Triple-Negative Breast Cancer

Breast cancer is the most common type of invasive cancer among women and the second leading cause of cancer death. The Centers for Disease Control and Prevention (“CDC”) estimates that there are approximately one million women in the United States living with breast cancer that has been diagnosed within the past five years. In 2019 there will be an estimated 271,270 new diagnoses and 42,260 breast cancer deaths in the United States each year and 12.4% of women will develop breast cancer in their lifetime. Effective therapies have been developed that target tumors containing at least one of three protein receptors: estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 (“HER2”).

Approximately 15% to 20% of breast cancers, however, do not express any of these three receptors and are referred to as triple-negative breast cancer (“TNBC”). These tumors have a more aggressive phenotype and a poorer prognosis due to the high propensity for metastatic progression and absence of specific targeted treatments. Prior to the recent anti-PD-L1 approval, the only approved targeted therapy for TNBC was olaparib (marketed as Lynparza) for the small minority of patients with mutations in the BRCA1 or BRCA2 genes. The five-year survival rate for TNBC has been reported to be 62.1%.