OSM

- Pioneering compounds believed to be the first orally administered reversible inhibitors to bind to and inhibit the SH2 domain potently and selectively - Proprietary STAT3 inhibitors are differentiated in several ways from alternative approaches, including potency, selectivity, reversibility and oral bioavailability Recludix Pharma, a leader in platform approaches to discover inhibitors of challenging targets for inflammatory disease and cancer, announced that in a presentation given today titled “Drugging the Undruggable,” Recludix’s senior vice president of biology, Paul Smith, Ph.D., discussed the first application of the company’s platform capabilities to target the Src Homology 2 (SH2) domain, as well as reviewed preclinical data on an early STAT3 inhibitor that was internally discovered through the platform. The presentation is available on the company’s website under the section titled “Events.” “We have had tremendous success in developing oral STAT inhibitors by targeting the SH2 domain, which has been previously considered undruggable,” said Nancy Whiting, PharmD, CEO of Recludix. “In this presentation, we highlight data from one of our earlier STAT3 discovery compounds showing its highly selective STAT3 inhibition with demonstrated potency in biochemical and cellular assays. We have continued to refine our lead STAT3 inhibitors and are in the final stages of confirming a STAT3 development candidate to move into clinical testing. We believe this could be a first- and best-in-class approach to selectively inhibit Th17-driven inflammatory diseases, such as psoriasis, rheumatoid arthritis, ulcerative colitis and Crohn's disease.” Recludix has generated potent and selective small molecule STAT3 inhibitors for Th17-driven inflammation. In T cell functional assays, Recludix’s STAT3 inhibitor potently and selectively impaired the Th17 phenotype, while still enabling the T cell to continue to perform robustly against viruses, bacteria, extracellular pathogens, and parasites. This is in contrast to the family of JAK or TYK2 inhibitors, which can be associated with changes in immune surveillance and hematopoiesis, leading to dose limiting safety concerns. Data demonstrate that targeting STAT3 spares interferon-driven anti-viral gene transcription and avoids STAT5 signaling, which is important for hematologic homeostasis and is differentiated from JAK/TYK2 inhibition. In a preclinical model of multiple sclerosis, proof-of-concept was established that STAT3 inhibition modulates in vivo Th17 diseases as measured by mean clinical score compared to vehicle control, exhibiting greater preclinical disease control than the JAK inhibitor baricitinib. Activity for STAT3 was found to be dose-dependent in both prophylactic and therapeutic preclinical models. Selective STAT3 inhibition was also evaluated in an imiquimod-induced (Th17-dependent) model of psoriasis which demonstrated that STAT3 inhibition modulates disease as measured by the PASI score and skin thickness, and it does so comparably to a supra-maximal efficacious dose of the JAK inhibitor tofacitinib (30 mg/kg). About STAT3 The interleukin cytokines IL-23 and IL-6 signal through STAT3 and promote the generation and function of pathogenic T helper type-17 (Th17) cells, a type of immune cell that is pro-inflammatory. Th17 cells are considered pivotal players in certain inflammatory diseases, including rheumatoid arthritis, psoriasis, inflammatory bowel disease and others. Inhibiting STAT3 can also offer potential efficacy beyond Th17 / IL-17 driven diseases in clinical indications where blocking the IL-6 pathway is clinically validated. Furthermore, clinical trials inhibiting oncostatin M (OSM) and IL-22, both STAT3 dependent cytokines, have been reported as efficacious in inflammatory disease. A selective, oral STAT3 inhibitor has potential to replace JAK/TYK2 inhibitors and biologics for multiple inflammatory diseases. STAT3 inhibitors may also have significant opportunity in cancer settings, as STAT3 is activated in greater than 70% of human cancers. About Recludix Recludix is a leader in developing platform approaches to discover potent and selective inhibitors of challenging protein targets. The company’s management team includes industry veterans with a track record of success, including former leaders and founding scientific team members of Seagen and Blueprint Medicines. Recludix has developed a unique drug discovery platform that integrates custom generated DNA-encoded libraries, massively parallel determination of structure activity relationships, and a proprietary screening tool to ensure selectivity. The company is employing this approach first in the development of SH2 domain inhibitors. Recludix’s most advanced programs are focused on STAT (signal transducer and activator of transcription) proteins where abnormal activation is found in inflammatory diseases, such as rheumatoid arthritis, asthma, atopic dermatitis, and inflammatory bowel disease, as well as numerous cancer types, such as multiple leukemias and lymphomas. The company has a strategic partnership with Sanofi for the development and commercialization of a STAT6 inhibitor. Recludix is also advancing STAT3 inhibitors for Th17-mediated I&I diseases and oncology indications, as well as additional programs. For more information, please visit the company’s website at https://recludixpharma.com. The content above comes from the network. if any infringement, please contact us to modify.

As parent company Roche aims to secure a place in the allogeneic CAR-T therapy race, Genentech is spinning its own deal to jump into fibrosis with a program from Kiniksa. Genentech shelled out $80 million in upfront cash and another $20 million in near-term payments to license Kiniksa’s vixarelimab, formerly known as KPL-716, and shepherd it into new clinical studies, the companies announced Wednesday. If all the milestones are achieved, Kiniksa could stand to gain another $600 million. Investor reaction to the deal was muted, as Kiniksa shares $KNSA were up about 1% in pre-market trading Wednesday. Seppi Lin, Genentech’s early development chief for ophthalmology, metabolism, neuroscience and immunology, tells Endpoints News in an email that the company intends to launch Phase II studies for vixarelimab in idiopathic pulmonary fibrosis/interstitial lung disease sometime in 2023. With the focus in IPF, the program will face a bit of a shift as Kiniksa had been developing vixarelimab primarily in prurigo nodularis, a chronic skin condition. The biotech had received breakthrough therapy designation in the indication in 2020, but Kiniksa now will not report data from a Phase IIb trial in prurigo nodularis patients, even though it plans to complete the study. Roche and Genentech pulled off the deal the same day the big Swiss conglomerate signed a new partnership with Poseida Therapeutics, placing a big bet on allogeneic CAR-T. Roche plunked down $220 million in upfront and near-term cash and is promising Poseida more than $6 billion in biobucks. Vixarelimab, meanwhile, is a monoclonal antibody that targets oncostatin M receptor beta, or OSMRβ, which Kiniksa says can affect the signaling of both IL-31 and oncostatin M, two cytokines implicated in fibrotic diseases. Kiniksa had started the Phase IIb trial in late 2020, aiming to test three dosing levels compared to placebo. A previous Phase IIa study met its primary endpoint in prurigo nodularis, Kiniksa said in April 2020. For Kiniksa, the deal will allow execs to continue pursuing other BD opportunities and provide runway into 2025, CEO Sanj Patel said on an investor call Wednesday morning. He declined to get into more specifics, however, saying only the company would be active in doing so in response to an analyst question. Editor’s note: This article has been updated to include comment from Genentech.

- Clinical data readouts expected throughout 2020 for rilonacept, mavrilimumab, KPL-716 and KPL-404 - - Year-end 2019 cash reserves of $233 million - HAMILTON, Bermuda, Feb. 26, 2020 (GLOBE NEWSWIRE) -- Kiniksa Pharmaceuticals, Ltd. (Nasdaq: KNSA) (“Kiniksa”), a biopharmaceutical company focused on discovering, acquiring, developing and commercializing therapeutic medicines for patients with significant unmet medical need, today reported fourth quarter and full-year 2019 financial results and highlighted recent pipeline activity. “We have the potential to generate data-driven value from multiple clinical-stage assets in 2020,” said Sanj K. Patel, Chief Executive Officer and Chairman of the Board of Kiniksa. “Near-term, given the anti-pruritic response shown in both cohorts of our KPL-716 Phase 1b study as well as recent external mechanistic validation, we are enabling an interim readout from our KPL-716 Phase 2a trial in prurigo nodularis. Data are expected by the end of April.” Pipeline Activity Rilonacept (IL-1α and IL-1β cytokine trap) Kiniksa is evaluating rilonacept for the potential treatment of recurrent pericarditis, a painful autoinflammatory cardiovascular disease. Kiniksa expects top-line data from RHAPSODY, a pivotal Phase 3 trial of rilonacept in patients with recurrent pericarditis, in the second half of 2020. Kiniksa recently announced the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy designation for rilonacept for the treatment of recurrent pericarditis. Kiniksa’s Breakthrough Therapy application was based on final data from an open-label Phase 2 clinical trial of rilonacept in a range of recurrent pericarditis populations. Kiniksa continues to prepare for the commercialization of rilonacept in recurrent pericarditis by generating evidence on unmet need and disease burden, building disease awareness with payers, physicians and advocacy groups, and establishing core capabilities such as distribution, patient services and data management. Kiniksa expects top-line data from RHAPSODY, a pivotal Phase 3 trial of rilonacept in patients with recurrent pericarditis, in the second half of 2020. Mavrilimumab (monoclonal antibody inhibitor targeting GM-CSFRα) Kiniksa is evaluating mavrilimumab for the potential treatment of giant cell arteritis (GCA), a chronic inflammatory disease of medium-to-large arteries. Kiniksa expects top-line data from a global Phase 2 proof-of-concept trial of mavrilimumab in patients with GCA in the second half of 2020. Kiniksa expects top-line data from a global Phase 2 proof-of-concept trial of mavrilimumab in patients with GCA in the second half of 2020. Kiniksa and Kite, a Gilead company, recently announced a clinical collaboration evaluating the investigational combination of axicabtagene ciloleucel and mavrilimumab in relapsed or refractory large B-cell lymphoma. The objective of the trial is to determine the effect of mavrilimumab on the safety of axicabtagene ciloleucel. Preclinical evidence shows the potential for interruption of granulocyte macrophage colony stimulating factor (GM-CSF) signaling to disrupt chimeric antigen receptor T (CAR T) cell-mediated inflammation without disrupting anti-tumor efficacy. The Phase 2 trial is expected to commence in the second half of 2020. KPL-716 (monoclonal antibody inhibitor of signaling through OSMRβ) Kiniksa is evaluating KPL-716 for the potential treatment of a variety of pruritic diseases, including prurigo nodularis, a chronic inflammatory skin condition. Kiniksa expects data from a Phase 2a trial of KPL-716 in patients with prurigo nodularis by the end of April 2020. Kiniksa expects interim data from cohorts of an exploratory Phase 2 trial of KPL-716 in diseases characterized by chronic pruritus in the first half of 2020. Kiniksa expects data from a Phase 2a trial of KPL-716 in patients with prurigo nodularis by the end of April 2020. Kiniksa expects interim data from cohorts of an exploratory Phase 2 trial of KPL-716 in diseases characterized by chronic pruritus in the first half of 2020. KPL-404 (monoclonal antibody inhibitor of signaling between CD40 and CD40L) Kiniksa is enrolling a single-ascending-dose Phase 1 clinical trial of KPL-404 in healthy volunteers. The first-in-human trial will provide safety data and pharmacokinetics as well as receptor occupancy and T-cell Dependent Antibody Response (TDAR). Top-line data are expected in the second half of 2020. Financial Results For the fourth quarter of 2019, Kiniksa reported a net loss of $31.8 million, compared to a net loss of $42.6 million for the fourth quarter of 2018. For the full-year 2019, Kiniksa reported a net loss of $161.9 million, compared to a net loss of $103.2 million for the full-year 2018. Total operating expenses for the fourth quarter of 2019 totaled $32.6 million, compared to $44.1 million for the fourth quarter of 2018. Non-cash share-based compensation expense totaled $5.0 million for the fourth quarter of 2019, compared to $2.6 million for the fourth quarter of 2018. Total operating expenses for the full-year 2019 totaled $170.0 million, compared to $108.2 million for the full-year 2018. Non-cash share-based compensation expense totaled $15.1 million for the full-year 2019, compared to $5.7 million for the full-year 2018. As of December 31, 2019, the company had cash, cash equivalents and short-term investments of $233.4 million and no outstanding debt. Financial Guidance Kiniksa expects that its cash, cash equivalents and short-term investments will fund its operating plan into the second half of 2021. Scientific Conference Presentations Kiniksa recently presented at the following scientific conferences: European Academy of Dermatology and Venerology (EADV) in October 2019; preclinical data from a longitudinal observational study in prurigo nodularis (LOTUS-PN). American Conference on Pharmacometrics (ACoP) in October 2019; pharmacokinetic/pharmacodynamic modeling for KPL-716. American College of Rheumatology (ACR) in November 2019; preclinical data analyzing the role of GM-CSF in GCA and showing mavrilimumab reduced arterial inflammation in an in vivo model. American Heart Association (AHA) in November 2019; final data from an open-label, multicenter Phase 2 clinical trial of rilonacept in a range of recurrent pericarditis populations. World Congress on Itch (WCI) in November 2019; preclinical data on the role of the oncostatin M (OSM) and interleukin-31 (IL-31) in the pathogenesis of prurigo nodularis. Kiniksa plans to present at the following scientific conference: American College of Cardiology (ACC) in March 2020; Phase 2 clinical data providing evidence of the potential for rilonacept to taper or obviate corticosteroid use in recurrent pericarditis. European Academy of Dermatology and Venerology (EADV) in October 2019; preclinical data from a longitudinal observational study in prurigo nodularis (LOTUS-PN). American Conference on Pharmacometrics (ACoP) in October 2019; pharmacokinetic/pharmacodynamic modeling for KPL-716. American College of Rheumatology (ACR) in November 2019; preclinical data analyzing the role of GM-CSF in GCA and showing mavrilimumab reduced arterial inflammation in an in vivo model. American Heart Association (AHA) in November 2019; final data from an open-label, multicenter Phase 2 clinical trial of rilonacept in a range of recurrent pericarditis populations. World Congress on Itch (WCI) in November 2019; preclinical data on the role of the oncostatin M (OSM) and interleukin-31 (IL-31) in the pathogenesis of prurigo nodularis. American College of Cardiology (ACC) in March 2020; Phase 2 clinical data providing evidence of the potential for rilonacept to taper or obviate corticosteroid use in recurrent pericarditis. About Kiniksa Kiniksa is a biopharmaceutical company focused on discovering, acquiring, developing and commercializing therapeutic medicines for patients suffering from debilitating diseases with significant unmet medical need. Kiniksa’s clinical-stage product candidates, rilonacept, mavrilimumab, KPL-716 and KPL-404, are based on strong biologic rationale or validated mechanisms, target underserved conditions and offer the potential for differentiation. These pipeline assets are designed to modulate immunological signaling pathways that are implicated across a spectrum of diseases. For more information, please visit www.kiniksa.com. About Rilonacept Rilonacept is a weekly, subcutaneously-injected, recombinant fusion protein that blocks interleukin-1 alpha (IL-1α) and interleukin-1 beta (IL-1β) signaling. Rilonacept was discovered and developed by Regeneron Pharmaceuticals, Inc. (Regeneron) and is approved by the FDA under the brand name ARCALYST® for the treatment of Cryopyrin-Associated Periodic Syndromes (CAPS), which includes Familial Cold Autoinflammatory Syndrome and Muckle-Wells Syndrome. Interleukin-1 (IL-1) blockade may interfere with immune response to infections. Serious, life-threatening infections have been reported in patients taking ARCALYST. ARCALYST should be discontinued if a patient develops a serious infection. Taking ARCALYST with tumor necrosis factor (TNF) inhibitors is not recommended because this may increase the risk of serious infections. Kiniksa exclusively licensed rilonacept from Regeneron for recurrent pericarditis and certain other indications. Rilonacept in recurrent pericarditis is an investigational drug. The FDA has granted Breakthrough Therapy designation to rilonacept for recurrent pericarditis. About Mavrilimumab Mavrilimumab is an investigational fully-human monoclonal antibody that is designed to antagonize GM-CSF signaling by binding to the alpha subunit of the GM-CSF receptor (GM-CSFRα). Kiniksa’s lead indication for mavrilimumab is GCA, an inflammatory disease of medium-to-large arteries. Additionally, Kiniksa and Kite have a clinical collaboration to evaluate mavrilimumab in combination with Yescarta® (axicabtagene ciloleucel) in patients with relapsed or refractory large B-cell lymphoma. About KPL-716 KPL-716 is an investigational fully-human monoclonal antibody that targets oncostatin M receptor beta (OSMRβ), which mediates signaling of IL-31 and OSM, two key cytokines implicated in pruritus, inflammation and fibrosis. Kiniksa believes KPL-716 to be the only monoclonal antibody in development that targets both pathways simultaneously. About KPL-404 KPL-404 is an investigational humanized monoclonal antibody that is designed to inhibit CD40-CD40 ligand (CD40L) interaction, a key T-cell co-stimulatory signal critical for B-cell maturation and immunoglobulin class switching. Kiniksa believes disrupting CD40-CD40L interaction is an attractive approach for blocking T-cell mediated, B-cell driven responses, drivers of multiple autoimmune disease pathologies such as rheumatoid arthritis, Sjogren’s syndrome, Graves’ disease, systemic lupus erythematosus and solid organ transplant. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. In some cases, you can identify forward looking statements by terms such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “potential” or “continue” or the negative of these terms or other similar expressions, although not all forward‑looking statements contain these identifying words. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation, statements regarding: our expectations for fiscal year 2020 data readouts; our beliefs about the mechanisms of action of our product candidates and potential impact of their approach; ; our clinical trial design; plans and timing to report or present preliminary, interim and final top-line or other clinical trial data and the potential impact of that data; and our projected timeframe for funding our operating plan with current cash, cash equivalents and short-term investments. These forward-looking statements are based on management’s current plans, estimates or expectations. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including without limitation, the following: potential delays or difficulty in enrollment of patients in, and activation or continuation of sites for, our clinical trials; potential complications in coordinating among requirements, regulations and guidelines of regulatory authorities across a number of jurisdictions for our global clinical trials; potential amendments to our clinical trial protocols initiated by us or required by regulatory authorities; potential delays or difficulty in completing our clinical trials, including as a result of our clinical trial design; potential for lower accrual of events in our clinical trials; potential undesirable side effects caused by our product candidates; our potential inability to demonstrate safety and efficacy to the satisfaction of applicable regulatory authorities or otherwise producing negative, inconclusive or commercially uncompetitive results; potential for changes between final data and any preliminary and interim top-line or other data we announce; impact of additional data from us or other companies; our potential inability to replicate in later clinical trials positive results from our earlier pre-clinical and clinical trials; drug substance and/or drug product shortages; our reliance on third parties as the sole source of supply of the drug substance and drug products used in our product candidates; our reliance on third parties to conduct our research, pre-clinical studies, clinical trials, and other trials for our product candidates; changes in our operating plan and funding requirements; substantial existing or new competition; and our ability to attract and retain qualified personnel. These and other important factors discussed under the caption “Risk Factors” in our Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on November 5, 2019 and our other reports subsequently filed with the SEC could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management’s plans, estimates, or expectations as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this press release. ARCALYST® is a registered trademark of Regeneron Pharmaceuticals, Inc. and Yescarta® is a registered trademark of Gilead Sciences, Inc., or its related companies. Every Second Counts!™ Kiniksa Investor and Media Contact Mark Ragosa (781) 430-8289 mragosa@kiniksa.com Source: Kiniksa Pharmaceuticals, Ltd.