MRGPRX2

– Subcutaneously administered AK006 showed approximately 77% bioavailability and prolonged receptor occupancy on mast cells – – Subcutaneous AK006 was well-tolerated with a favorable safety profile – – Top-line Phase 1 results of Intravenous AK006 in patients with CSU are expected in early Q1 of 2025 – SAN CARLOS, Calif., Oct. 10, 2024 (GLOBE NEWSWIRE) -- Allakos Inc. (Nasdaq: ALLK), a biotechnology company developing AK006 for the treatment of mast cell-driven diseases, today announced results from the Phase 1 study of subcutaneous AK006 in healthy volunteers. AK006 is a Siglec-6 monoclonal antibody that selectively inhibits mast cells. Inappropriate activation of mast cells has been identified as a pathogenic driver of multiple diseases, including chronic spontaneous urticaria, food allergy and asthma. Phase 1 Study Results of Subcutaneous AK006 in Healthy Volunteers Bioavailability of subcutaneous AK006 was approximately 77%. Subcutaneous administered AK006 showed an estimated half-life of 12-22 days. Consistent with the IV formulation, skin biopsies taken from subcutaneous AK006 treated healthy volunteers showed high levels of receptor occupancy confirming AK006 reaches skin tissue mast cells. The 720 mg dose of AK006 showed 98% receptor occupancy at day 113 suggesting the potential for infrequent dosing. Single and multiple doses of IV AK006 and single dose subcutaneous AK006 up to 720 mg were well-tolerated with a favorable safety profile. In the safety pro date: There were no serious adverse events (SAEs) in subjects on AK006. There were no treatment emergent adverse events leading to discontinuation of AK006. There were no dose limiting toxicities. The most common adverse events (≥10%) occurring more frequently in subjects on AK006 were headache and dysmenorrhea, all of which were mild-to-moderate in severity. Phase 1 AK006 Study in Healthy Volunteers and in Patients with Chronic Spontaneous Urticaria AK006 is being studied in an ongoing Phase 1 single ascending dose (SAD) and multiple ascending dose (MAD) trial that includes a randomized, double-blind, placebo-controlled CSU arm (NCT06072157). In June 2024 the company reported data from the SAD and MAD IV cohorts of the study. The data announced today are from the randomized, double-blind, placebo-controlled SAD subcutaneous cohorts of the study. In these cohorts, healthy volunteers were randomized 6:2 to receive doses of subcutaneous AK006 or placebo. Two dosed levels, 150 mg and 720 mg, of subcutaneous AK006 were tested. The primary objective was to evaluate the safety and tolerability of single subcutaneous doses of AK006 in healthy volunteers, establish the bioavailability and pharmacokinetics of subcutaneous AK006, and to explore Siglec-6 receptor occupancy on mast cells in skin biopsy samples. In the CSU arm of the Phase 1 study, up to 60 adult patients with antihistamine refractory CSU (including patients with prior biologics treatment), will be randomized 2:1 to receive 720 mg of IV AK006 or placebo once every four weeks (Q4W). The primary efficacy analysis will be the change in the urticaria activity score (UAS7) at week 14. Data from approximately 30 patients is expected in early Q1 of 2025. About AK006 AK006 is a humanized IgG1 monoclonal antibody which activates the inhibitory receptor Siglec-6. Siglec-6 is found on the surface of mature mast cells and offers a way to selectively target mast cells. In preclinical experiments, AK006 inhibits IgE-dependent and IgE-independent mast cell activation including activation through IgE, MRGPRX2 and KIT receptors. In these experiments, AK006 drives deep mast cell inhibition and, in addition to its inhibitory activity, can reduce mast cell numbers via antibody-dependent cellular phagocytosis in the presence of activated macrophages. About Allakos Allakos is a clinical stage biotechnology company developing therapeutics that target immunomodulatory receptors present on immune effector cells involved in allergy, inflammatory and proliferative diseases. Activating these immunomodulatory receptors allows for the direct targeting of cells involved in disease pathogenesis and, in the setting of allergy and inflammation, has the potential to result in broad inhibition of inflammatory cells. The Company’s most advanced antibody in ongoing clinical development is AK006. AK006 targets Siglec-6, an inhibitory receptor expressed on mast cells. Mast cells are widely distributed in the body and play a central role in the inflammatory response. Inappropriately activated mast cells have been identified as key drivers in a number of severe diseases affecting the gastrointestinal tract, eyes, skin, lungs and other organs. In preclinical studies, AK006 appears to provide deep mast cell inhibition and, in addition to its inhibitory activity, reduce mast cell numbers. For more information, please visit the Company’s website at Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 as contained in Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Such forward-looking statements include, but are not limited to, Allakos’ progress, business plans, areas of focus and preclinical research; enrollment in Allakos’s clinical study; timing and availability of data; the potential of AK006; and Allakos’ anticipated milestones. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from current expectations and beliefs, including but not limited to: Allakos’ stages of clinical drug development; Allakos’ ability to timely initiate and complete clinical trials for AK006; Allakos’ ability to obtain required regulatory approvals for its clinical trials; uncertainties related to the enrollment of patients in its clinical trials; Allakos’ ability to demonstrate sufficient safety and efficacy of its product candidates in its clinical trials; uncertainties related to the success of clinical trials, regardless of the outcomes of preclinical testing or early-stage trials; Allakos’ ability to advance additional product candidates beyond AK006; uncertainties related to Allakos’ ability to realize the contemplated benefits of its restructuring and related reduction in force; Allakos’ ability to accurately forecast financial results; Allakos’ ability to obtain additional capital to finance its operations, research and drug development; general economic and market conditions, both domestic and international; domestic and international regulatory obligations; and other risks. Information regarding the foregoing and additional risks may be found in the section entitled “Risk Factors” in documents that Allakos files from time to time with the SEC. These documents contain and identify important factors that could cause the actual results for Allakos to differ materially from those contained in Allakos’ forward-looking statements. Any forward-looking statements contained in this press release speak only as of the date hereof, and Allakos specifically disclaims any obligation to update any forward-looking statement, except as required by law. These forward-looking statements should not be relied upon as representing Allakos’ views as of any date subsequent to the date of this press release. Source: Allakos Inc. Investor Contact: Adam Tomasi, President Alex Schwartz, VP Strategic Finance and Investor Relations ir@allakos.com Media Contact: Denise Powell denise@redhousecomms.com

PALO ALTO, CA, USA I September 3, 2024 I Evommune, Inc., a clinical stage biotechnology company discovering and developing new ways to treat immune-mediated inflammatory diseases, today announced the enrollment of the first patient in a Phase 2 trial of EVO756 in adults with CIndU. EVO756 is a potent, highly selective small molecule antagonist of mas-related G-protein coupled receptor X2 (MRGPRX2) and represents a new, targeted approach with the potential for once-daily oral administration without the serious side effects observed with other therapies. “As we continue to execute on our clinical development plans for EVO756, we are commencing this Phase 2 trial in 15 study sites across the United States. CIndU patients have limited treatment options, and we believe a novel, highly potent, selective agent, that can be orally administered once daily, could provide patients with major therapeutic benefit,” said J. Mark Jackson, MD, Vice President, Clinical Development at Evommune. The multi-center trial is designed to evaluate the safety and efficacy of EVO756 in approximately 30 patients with either symptomatic dermographism or cold urticaria, the two most common forms of CIndU. Efficacy endpoints include changes from baseline in disease specific provocation thresholds that are used as objective markers to quantify disease severity and response to treatment. EVO756 will be administered orally, once daily, for four weeks, and will be evaluated for safety and efficacy at weekly visits during treatment, with patients serving as their own control. “Initiation of this trial marks another important milestone in dedication to delivering the therapeutic potential of MRGPRX2 antagonism to patients in a broad range of mast cell-mediated disorders,” said Daniel J. Burge, M.D., Senior Vice President, Clinical Development at Evommune. “Following the success of our proof-of-concept study with EVO756 earlier this year, we are also on track to initiate a Phase 2b trial in chronic spontaneous urticaria in the second quarter of 2025.” About Chronic Urticaria Chronic urticaria, defined as urticaria persisting for more than 6 weeks, is a substantial burden for patients, their families and careers, the healthcare system, and society. Chronic urticaria manifests with very itchy hives that may vary in size and can result in sleep deprivation, anxiety, depression, lack of energy, and social isolation which can result in a significant deterioration in the quality of life. Some patients with chronic urticaria may also develop swelling deeper under the skin or in other tissues (angioedema). There are two main forms of chronic urticaria. In chronic spontaneous urticaria (CSU), hives occur spontaneously, without known triggers. In chronic inducible urticaria (CIndU), hives are induced by specific triggers such as cold exposure (cold urticaria) or touch (symptomatic dermographism), among others. Chronic urticaria is a mast cell-driven disease. Activated mast cells release histamine along with other mediators, such as platelet-activating factor and cytokines, resulting in sensory nerve activation, vasodilation, plasma extravasation, and recruitment of cells to the urticarial lesion. About EVO756 EVO756 is a potent, highly selective small molecule antagonist of mas-related G-protein coupled receptor X2 (MRGPRX2). MRGPRX2 is most abundantly found on mast cells and peripheral sensory neurons. MRGPRX2 can trigger IgE-independent activation (degranulation) via multiple ligands, which can lead to a variety of symptoms depending on the tissue that is affected. Evommune’s pre-clinical data demonstrates that by blocking activation of MRGPRX2 via all disease relevant ligand categories, EVO756 can prevent the degranulation of mast cells. EVO756 has the potential to be a first-in-class oral treatment for a variety of mast cell mediated diseases. In addition, due to its unique function on peripheral sensory neurons, EVO756 could provide fast relief of itch associated with inflammatory diseases, such as atopic dermatitis. About Evommune, Inc. Evommune, Inc., a Palo Alto based biotech company, is creating game-changing science to treat immune-mediated inflammatory diseases by discovering, developing, and delivering therapies that address symptoms and halt progressive disease. For more information, please visit www.evommune.com . SOURCE: Evommune

PHILADELPHIA, July 31, 2024 /PRNewswire/ -- Mast cells are found throughout the body close to blood vessels and are packed with granules containing the immune signaling compound histamine, and enzymes that attack pathogens and promote white blood cell recruitment. When triggered by a perceived threat, mast cells expel their contents. This activity protects against infection and aids healing, but it has also made mast cells infamous for driving allergic asthma and inflammatory skin disorders, such as rosacea and contact dermatitis. Despite their prominence, few researchers study these scarce and difficult-to-work-with cells. Hydar Ali, a professor in the Department of Translational Sciences at Penn Dental Medicine, belongs to a select group who focus on mast cells. His research explores how they function to protect the body and how things can go wrong. "These cells are relatively poorly understood, and yet we've been able to identify some of the most sought-after molecular targets to affect diseases like allergies and asthma that have the potential to kill," Ali says. He and his colleagues discovered a receptor, known as MRGPRX2, that only appears on mast cells. This research led them to find that small proteins called antimicrobial peptides could activate mast cells through MRGPRX2 to harness their protective function and help clear pathogens. In the context of an allergic response, however, he has shown that this receptor drives problematic inflammation. "It's two sides of the same coin," Ali says. More recently, his team has investigated mast cells' role in systemic allergic reactions that can lead patients to stop using the multiple sclerosis drug glatiramer acetate. Their experiments demonstrated that this medication activates MRGPRX2 receptors causing mast cells to expel histamine and their other contents, results suggesting MRGPRX2 inhibitors could treat these reactions and help patients remain on the medication. His lab is also investigating this receptor's role in periodontal disease, an inflammatory condition that damages the gums and connective tissue of the mouth. Their experiments have shown, for example, that mast cells expressing MRGPRX2 become more abundant in chronic periodontitis, the more severe form of the condition. Ultimately, he hopes to study the potential for MRGPRX2 blockers to reduce inflammation in periodontitis. Media Contact: Beth Adams, [email protected] SOURCE PENN DENTAL MEDICINE