Syk x JAK

Existing cash to fund planned ongoing operations into mid-2026 AK006 is being tested in a comprehensive Phase 1 clinical program, including: ongoing single and multiple ascending dose trial in healthy volunteers a randomized, double-blind, placebo-controlled trial in patients with CSU a subcutaneous AK006 Phase 1 PK and bioavailability trial Management to host conference call and webcast today at 8:00 am E.T. SAN CARLOS, Calif., Jan. 16, 2024 (GLOBE NEWSWIRE) -- Allakos, Inc. (the Company) (Nasdaq: ALLK), a biotechnology company developing antibodies for the treatment of allergic, inflammatory and proliferative diseases, today announced a restructuring to reduce costs and to focus on AK006 clinical development and additional preclinical programs. As a result, the Company’s cash runway is expected to extend into mid-2026. Restructuring Activities The Company will halt lirentelimab-related activities across clinical, manufacturing, research and administrative functions. As a result, the Company will reduce its workforce by approximately 50%. Cash Guidance The Company ended the fourth quarter of 2023 with approximately $171 million in cash, cash equivalents and investments (unaudited). The Company’s outlook for 2024 cash, cash equivalents and investments is as follows: Cash, cash equivalents and investments at year end 2023 (unaudited) $171 million Estimated 2024 net cash used in operating activities (GAAP) ($85 to $90 million) Estimated cash, cash equivalents and investments at year end 2024 $81 to $86 million Components of estimated 2024 net cash used in operating activities for the year ended December 31, 2024 are as follows: Estimated net cash used in operating activities (GAAP) $85 to $90 million Less: estimated lirentelimab closeout, severance and other costs 1 ($30 million) Estimated adjusted net cash used in operating activities (non-GAAP) $55 to $60 million 1 The Company anticipates that the significant majority of the restructuring expenditures will be paid in the first half of 2024. The Company expects that the restructuring activities will extend the cash runway into mid-2026. Anticipated Allakos Milestones Q1 2024: Complete dosing in the single ascending dose (SAD) and multiple ascending dose (MAD) cohorts of the randomized, double-blind, placebo-controlled Phase 1 trial of Intravenous (IV) AK006 in healthy volunteers. Q1 2024: Initiate the randomized, double-blind, placebo-controlled subcutaneous (SC) AK006 cohort in healthy volunteers. Q2 2024: Report SAD and MAD safety, pharmacokinetics (PK), and pharmacodynamic (PD) results from the Phase 1 IV AK006 trial in healthy volunteers, including data to confirm Siglec-6 receptor occupancy in skin biopsy samples. Q2 2024: Initiate the randomized, double-blind, placebo-controlled Phase 1 trial of IV AK006 in patients with chronic spontaneous urticaria (CSU). Q3 2024: Report subcutaneous (SC) AK006 safety, PK, and PD results from the Phase 1 trial in healthy volunteers, including data to confirm Siglec-6 receptor occupancy in skin biopsy samples. Year End 2024: Report topline data from the Phase 1 trial of IV AK006 in patients with CSU. About Siglec-6 and AK006 Siglec-6 is a member of the family of cell surface receptors called Sialic acid-binding immunoglobulin-type lectins (Siglecs). Siglec-6 is found on the surface of mature mast cells, and therefore offers a way to target mast cells. Siglec-6 exerts inhibition through its intracellular immunoreceptor tyrosine-based motif (ITIM). ITIM bearing receptors antagonize activating receptors and consequently have important roles in regulating the immune system. The inhibitory function is derived from the ability of the ITIMs to recruit SH2 domain-containing phosphatases which work to oppose activating signals driven by kinase signaling cascades. Disrupting kinase signaling cascades has been a successful strategy for treating inflammatory diseases as evidenced by approved drugs which target JAK, KIT, BTK, SYK, and others. However, often these kinase signaling pathways are active in multiple cell types, which can result in unintended side effects when disrupted. AK006 is a humanized IgG1 monoclonal antibody which activates the inhibitory receptor Siglec-6. AK006 is directed to an extracellular epitope of the Siglec-6 receptor that was identified for its ability to generate strong inhibitory signals to mast cells. Furthermore, AK006 was engineered to have higher cell surface residence time which may increase mast cell inhibition. In addition to inhibition, in preclinical studies AK006 reduces mast cell numbers via antibody-dependent cellular phagocytosis (ADCP) in the presence of activated macrophages. Conference Call and Webcast Information The webcast and conference call will take place at 8:00 am ET / 5:00 am PT on January 16th, 2024. Please click here to pre-register to participate in the conference call and obtain your dial in number and PIN. A webcast of the live call will be available online in the investor relations section of the Allakos website. Access to the webcast replay will be available approximately two hours after completion of the call and will be archived on the Company’s website for approximately 30 days. About Allakos Allakos is a clinical stage biotechnology company developing therapeutics which 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 . Non-GAAP Financial Measure In this press release, Allakos’ estimated net cash used in operating activities is provided in accordance with generally accepted accounting principles (GAAP) in the United States and also on a non-GAAP basis. Non-GAAP estimated adjusted net cash used in operating activities excludes estimated lirentelimab closeout, severance and other costs. Non-GAAP estimated adjusted net cash used in operating activities is provided as a complement to estimated net cash used in operating activities provided in accordance with GAAP because management believes the non-GAAP financial measure is useful to investors in assessing the Company’s operating performance. Management also uses the non-GAAP financial measure to establish operational goals that are communicated internally and externally, to manage the Company’s business and to evaluate its performance. 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 and areas of focus; Allakos’ expectations regarding its financial position and guidance, including estimated lirentelimab closeout, severance and other costs and the timing of payment of restructuring expenditures, ending 2023 and 2024 cash, cash equivalents and investments, and cash runway; 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; 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 to 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

Finalized Dose Escalation/Dose Exploration Trial in 77 R/R AML PatientsFavorable safety with monotherapy responses across four dose levels with no DLT in mutationally diverse and difficult to treat R/R AML PopulationsTP53MUT CR/CRh = 20% │ RASMUT CR/CRh = 22% Completed Successful Type B EOP1 Meeting with US FDAMonotherapy RP2D selected as 80mg daily and single arm accelerated path remains open Initiated APTIVATE Expansion Trial with R/R AMLTuspetinib monotherapy and Tuspetinib + Venetoclax (TUS/VEN) doublet show brisk enrollmentTUS/VEN doublet well tolerated, all patients remain on study, preliminary CR activity reported among first patients treated SAN DIEGO and TORONTO, June 10, 2023 (GLOBE NEWSWIRE) -- Aptose Biosciences Inc. (“Aptose” or the “Company”) (NASDAQ: APTO, TSX: APS), a clinical-stage precision oncology company developing highly differentiated oral kinase inhibitors to treat hematologic malignancies, today released highlights from a clinical update event held today, June 10, 2023, in conjunction with EHA 2023 International Congress of the European Hematology Association in Frankfurt, Germany. The event included an up-to-date review of clinical data for Aptose’s two investigational products under development for hematologic malignancies: tuspetinib, an oral, myeloid kinase inhibitor in the Phase 1/2 APTIVATE trial in patients with relapsed or refractory acute myeloid leukemia (AML); and luxeptinib, an oral, dual lymphoid and myeloid kinase inhibitor in Phase 1 a/b stage development for the treatment of patients with relapsed or refractory hematologic malignancies. The webcast of the presentation is available on Aptose’s website here. Aptose provided updated clinical findings with tuspetinib, a potent suppressor of FLT3, SYK, JAK 1/2, mutant forms of cKIT, and the RSK1/2 kinases operative in AML: Completed tuspetinib dose escalation and dose exploration Phase 1/2 trial in 77 R/R AML patients. Tuspetinib demonstrated a favorable safety profile.Tuspetinib delivered monotherapy responses across four dose levels with no DLT in mutationally diverse and difficult to treat R/R AML populations, including TP53-mutated patients with a CR/CRh = 20% and RAS-mutated patients with a CR/CRh = 22%. Completed successful End of Phase 1 (EOP1) Meeting with US FDA for tuspetinib, and a monotherapy RP2D was selected as 80mg daily, and all development paths remain open, including the single arm accelerated path.Initiated tuspetinib APTIVATE expansion trial with R/R AML patients. Tuspetinib is being administered as a monotherapy and as a combination doublet with tuspetinib + venetoclax (TUS/VEN), and enrollment has been brisk.TUS/VEN doublet has been well tolerated, all patients remain on study, and preliminary CR activity has already been reported in patients previously treated with VEN. Aptose also reviewed clinical findings with the new G3 formulation of luxeptinib (Lux): 50mg G3 formulation with continuous dosing achieves roughly equivalent PK profile as 900mg original G1 formulation.Expect to dose escalate G3 formulation with continuous dosing in patients soon. “We are delighted to have finalized our dose escalation and dose exploration Phase 1/2 trial with tuspetinib (TUS), to have demonstrated single agent responses across four dose levels that had no DLTs and across a range of R/R AML populations with a diversity of adverse mutations,” said William G. Rice, Ph.D., Chairman, President and Chief Executive Officer. “As part of our EOP1 meeting with the FDA, we designated 80mg daily as our monotherapy recommended phase 2 dose (RP2D), and now we focus all attention on our APTIVATE expansion trial to place monotherapy TUS in more patients with highly adverse mutations and to evaluate TUS in combination with venetoclax (VEN) as a doublet in R/R AML patients. Notably, to date, the doublet appears to be well tolerated, with all patients remaining on study, including a preliminary CR in a R/R AML patient who previously failed venetoclax. We look forward to accelerating testing of the doublet, adding MDS patients to our APTIVATE trial, and with the aim of moving into triplet therapy (TUS/VEN/HMA) in 1L AML patients.” About Aptose Aptose Biosciences is a clinical-stage biotechnology company developing precision medicines addressing unmet medical needs in oncology, with an initial focus on hematology. The Company's small molecule cancer therapeutics pipeline includes products designed to provide single agent efficacy and to enhance the efficacy of other anti-cancer therapies and regimens without overlapping toxicities. The Company has two clinical-stage oral kinase inhibitors under development for hematologic malignancies: tuspetinib (HM43239), an oral, myeloid kinase inhibitor being studied as monotherapy and in combination therapy in the APTIVATE international Phase 1/2 expansion trial in patients with relapsed or refractory acute myeloid leukemia (AML); and luxeptinib (CG-806), an oral, dual lymphoid and myeloid kinase inhibitor in Phase 1 a/b stage development for the treatment of patients with relapsed or refractory hematologic malignancies. For more information, please visit www.aptose.com. Forward Looking Statements This press release may contain forward-looking statements within the meaning of Canadian and U.S. securities laws, including, but not limited to, statements relating to the therapeutic potential of tuspetinib, its clinical development and safety profile, as well as statements relating to the Company’s plans, objectives, expectations and intentions and other statements including words such as “continue”, “expect”, “intend”, “will”, “should”, “would”, “may”, and other similar expressions. Such statements reflect our current views with respect to future events and are subject to risks and uncertainties and are necessarily based upon a number of estimates and assumptions that, while considered reasonable by us are inherently subject to significant business, economic, competitive, political and social uncertainties and contingencies. Many factors could cause our actual results, performance or achievements to be materially different from any future results, performance or achievements described in this press release. Such factors could include, among others: our ability to obtain the capital required for research and operations and to continue as a going concern; the inherent risks in early stage drug development including demonstrating efficacy; development time/cost and the regulatory approval process; the progress of our clinical trials; our ability to find and enter into agreements with potential partners; our ability to attract and retain key personnel; changing market conditions; inability of new manufacturers to produce acceptable batches of GMP in sufficient quantities; unexpected manufacturing defects; and other risks detailed from time-to-time in our ongoing quarterly filings, annual information forms, annual reports and annual filings with Canadian securities regulators and the United States Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should the assumptions set out in the section entitled "Risk Factors" in our filings with Canadian securities regulators and the United States Securities and Exchange Commission underlying those forward-looking statements prove incorrect, actual results may vary materially from those described herein. These forward-looking statements are made as of the date of this press release and we do not intend, and do not assume any obligation, to update these forward-looking statements, except as required by law. We cannot assure you that such statements will prove to be accurate as actual results and future events could differ materially from those anticipated in such statements. Investors are cautioned that forward-looking statements are not guarantees of future performance and accordingly investors are cautioned not to put undue reliance on forward-looking statements due to the inherent uncertainty therein. For further information, please contact: Aptose Biosciences Inc.Susan PietropaoloInvestor Relations201-923-2049spietropaolo@aptose.comLifeSci Advisors, LLC Dan Ferry, Managing Director617-430-7576Daniel@LifeSciAdvisors.com

EHA Abstract on Tuspetinib and Venetoclax Recently PublishedSAN DIEGO and TORONTO, May 31, 2023 (GLOBE NEWSWIRE) -- Aptose Biosciences Inc. (“Aptose” or the “Company”) (NASDAQ: APTO, TSX: APS), a clinical-stage precision oncology company developing highly differentiated oral targeted agents to treat hematologic malignancies, announced today that the company management team will provide a clinical update on Saturday, June 10, 2023, at 12:00 PM EST / 6:00 PM CEST, in conjunction with EHA 2023 International Congress of the European Hematology Association in Frankfurt, Germany. The webcast event will include an interim review of Aptose’s lead compound tuspetinib, a myeloid kinase inhibitor, currently being tested as a monotherapy and in combination with venetoclax in the phase 1/2 APTIVATE trial. Tuspetinib, administered as a once-daily oral tablet, is a precision targeted kinase inhibitor designed to suppress a select handful of kinases known to drive proliferation of acute myeloid leukemia (AML) while maintaining a favorable safety profile. Aptose management will highlight additional insights from the completed Phase 1/2 dose escalation clinical trial of tuspetinib and review early trends from the ongoing APTIVATE trial. Aptose Clinical Update Webcast Details Date & Time: Saturday, June 10, 2023, 12:00 PM ET Participant Webcast Link: Link Participant Dial-in: Toll Free Investors Dial: 1-877-407-9039 Toll/International Investors Dial: 1-201-689-8470 Conference ID: 13739137 The slides will be available on Aptose’s website here and the webcast of the presentation will be archived shortly after the conclusion of the event. In addition, an abstract on tuspetinib was recently published in EHA’s open access library here: Abstract: PB1766 Title: IN VITRO ACQUIRED RESISTANCE TO THE ORAL MYELOID KINASE INHIBITOR TUSPETINIB CREATES SYNTHETIC LETHAL VULNERABILITY TO VENETOCLAX Session Title: Acute myeloid leukemia - Biology & Translational Research Tuspetinib (TUS) is a once daily, oral agent that potently inhibits JAK1/2, SYK, RSK1/2, wildtype and mutant forms of FLT3, and mutant forms of KIT kinases, thereby simultaneously suppressing multiple oncogenic signaling pathways that mediate resistance to various drugs. TUS as a single agent has generated complete remissions in relapsed/refractory (R/R) acute myeloid leukemia (AML) patients with diverse mutations and demonstrated favorable safety in a Phase 1 trial (NCT03850574). TUS is now in a Phase 1/2 expansion trial (APTIVATE) for R/R AML patients with high unmet need as a monotherapy and as a doublet in combination with venetoclax. The clinical activity against diverse mutational subpopulations led us to investigate alterations in AML cells that may give rise to TUS resistance, and to understand the sensitivity of resistant isolates to venetoclax and other agents used to treat AML. Resistance to TUS in MOLM-14 cells required prolonged high-level drug exposure, but ultimately yielded a stable phenotype. Strikingly, acquired TUS resistance generated a synthetic lethal vulnerability in which the cells were unusually hypersensitive to venetoclax. This suggests that concurrent administration of TUS and venetoclax may be advantageous clinically as TUS and venetoclax could act in concert to discourage the emergence of drug resistance during treatment. For full published abstract, please visit: https://library.ehaweb.org/eha/2023/eha2023-congress/386894/himangshu.sonowal.in.vitro.acquired.resistance.to.the.oral.myeloid.kinase.html About Aptose Aptose Biosciences is a clinical-stage biotechnology company developing precision medicines addressing unmet medical needs in oncology, with an initial focus on hematology. The Company's small molecule cancer therapeutics pipeline includes products designed to provide single agent efficacy and to enhance the efficacy of other anti-cancer therapies and regimens without overlapping toxicities. The Company has two clinical-stage oral kinase inhibitors under development for hematologic malignancies: tuspetinib (HM43239), an oral, myeloid kinase inhibitor being studied as monotherapy and in combination therapy in the APTIVATE international Phase 1/2 expansion trial in patients with relapsed or refractory acute myeloid leukemia (AML); and luxeptinib (CG-806), an oral, dual lymphoid and myeloid kinase inhibitor in Phase 1 a/b stage development for the treatment of patients with relapsed or refractory hematologic malignancies. For more information, please visit www.aptose.com. Forward Looking Statements This press release may contain forward-looking statements within the meaning of Canadian and U.S. securities laws, including, but not limited to, statements relating to the therapeutic potential of tuspetinib and its clinical development as well as statements relating to the Company’s plans, objectives, expectations and intentions and other statements including words such as “continue”, “expect”, “intend”, “will”, “should”, “would”, “may”, and other similar expressions. Such statements reflect our current views with respect to future events and are subject to risks and uncertainties and are necessarily based upon a number of estimates and assumptions that, while considered reasonable by us are inherently subject to significant business, economic, competitive, political and social uncertainties and contingencies. Many factors could cause our actual results, performance or achievements to be materially different from any future results, performance or achievements described in this press release. Such factors could include, among others: our ability to obtain the capital required for research and operations and to continue as a going concern; the inherent risks in early stage drug development including demonstrating efficacy; development time/cost and the regulatory approval process; the progress of our clinical trials; our ability to find and enter into agreements with potential partners; our ability to attract and retain key personnel; changing market conditions; inability of new manufacturers to produce acceptable batches of GMP in sufficient quantities; unexpected manufacturing defects; and other risks detailed from time-to-time in our ongoing quarterly filings, annual information forms, annual reports and annual filings with Canadian securities regulators and the United States Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should the assumptions set out in the section entitled "Risk Factors" in our filings with Canadian securities regulators and the United States Securities and Exchange Commission underlying those forward-looking statements prove incorrect, actual results may vary materially from those described herein. These forward-looking statements are made as of the date of this press release and we do not intend, and do not assume any obligation, to update these forward-looking statements, except as required by law. We cannot assure you that such statements will prove to be accurate as actual results and future events could differ materially from those anticipated in such statements. Investors are cautioned that forward-looking statements are not guarantees of future performance and accordingly investors are cautioned not to put undue reliance on forward-looking statements due to the inherent uncertainty therein. For further information, please contact: Aptose Biosciences Inc.LifeSci Advisors, LLCSusan Pietropaolo Dan Ferry, Managing DirectorInvestor Relations617-430-7576201-923-2049Daniel@LifeSciAdvisors.comspietropaolo@aptose.com