MNK1 inhibitors(MAP kinase-interacting serine/threonine-protein kinase MNK1 inhibitors), MNK2 inhibitors(MAP kinase-interacting serine/threonine-protein kinase 2 inhibitors)

Therapeutic Areas

NeoplasmsImmune System DiseasesDigestive System Disorders+ [3]

Active Indication

Non-Small Cell Lung CancerPD-L1 positive Lung CancerBreast Cancer+ [4]

Inactive Indication

Advanced breast cancerAdvanced Hepatocellular CarcinomaAdvanced Malignant Solid Neoplasm+ [3]

Originator Organization

eFFECTOR Therapeutics Operations, Inc.

Active Organization

eFFECTOR Therapeutics, Inc.

eFFECTOR Therapeutics Operations, Inc.Merck Serono SA

+ [1]

Inactive Organization-

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

Structure/Sequence

Molecular FormulaC17H20N6O2

InChIKeyHKTBYUWLRDZAJK-UHFFFAOYSA-N

CAS Registry1849590-01-7

View All Structures (2)

Clinical Trials associated with Tomivosertib

NCT05744739

/ Active, not recruitingPhase 1IIT

Phase 1 Dose Escalation Study of Tomivosertib in Relapsed or Refractory Acute Myeloid Leukemia (AML)

Phase 1 of the study will open first with a (Bayesian optimal interval BOIN) dose finding design. The starting dose of tomivosertib is 100mgdaily (doses 24 ± 2 hours apart), PO, self-administered with meals. The dose finding follows a BOIN design, with the 100mg BID dose level with a meal being the highest dose. There is one dose level below (dose level -1 = 100mg QD without a meal) that will be given if the de-escalation condition is met during dose finding. Upon completion of the phase 1 dose finding portion of the study, the recommended starting dose of tomivosertib for the subsequent combination with the other agents will be determined, as described in Section 4.3 and Section 8.0.
Tomivosertib will be dosed continuously on days 1-28 of each 28-day cycle at the dose level assigned for that cohort.

Start Date29 Sep 2023

Sponsor / Collaborator

Northwestern University

[+2]

NCT04622007

/ Active, not recruitingPhase 2

A Randomized, Double-Blind, Placebo-Controlled Trial of Tomivosertib in Combination With Anti-PD-(L)1 Therapy in Subjects With NSCLC as First Line Therapy or When Progressing on Single-Agent First-Line Anti PD (L)1 Therapy

Tomivosertib combined with pembrolizumab in Subjects with PD-L1 positive NSCLC

Start Date02 Jun 2021

Sponsor / Collaborator

eFFECTOR Therapeutics Operations, Inc.

[+2]

NCT04261218

/ CompletedPhase 1IIT

A Trial to Assess the Safety, Pharmacodynamic Effects, Pharmacokinetics and Efficacy of the MNK Inhibitor Tomivosertib (eFT508) in Combination With Paclitaxel, Following a Run-in Period of Tomivosertib Monotherapy, in Patients With Advanced Breast Cancer

This is a multicenter, open-label trial to evaluate the safety, pharmacodynamics (PD), pharmacokinetics (PK), and efficacy of tomivosertib in combination with paclitaxel in patients with advanced breast cancer (ABC) of any subtype.
The trial will enroll up to 45 patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2 with any breast cancer (BC) subtype and at least one measurable lesion, for whom standard-of-care treatments are ineffective, not tolerated or were refused.
All patients will be initially treated with tomivosertib for 14 days (referred as the run-in period). Once treatment samples are obtained, weekly paclitaxel will be added to the treatment regimen.
Tumor assessments will be done at screening and then periodically throughout trial treatment. Patients will continue to receive trial treatment until progressive disease, as defined according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, intolerable trial-treatment-related toxicity, consent withdrawal, or other criteria is met (defined within the trial protocol).

Start Date25 Aug 2020

Sponsor / Collaborator

Translational Research In Oncology

[+2]

100 Clinical Results associated with Tomivosertib

100 Translational Medicine associated with Tomivosertib

100 Patents (Medical) associated with Tomivosertib

Literatures (Medical) associated with Tomivosertib

04 Mar 2025·Expert Opinion on Therapeutic Patents

A patent review of mitogen-activated protein kinase-interacting kinases (MNKs) modulators (2019–present)

Review

Author: Chen, Xiang ; Li, Qiang ; Guo, Yue-Wei ; Jin, Xin ; Su, Mingzhi

INTRODUCTIONThe mitogen-activated protein kinase interacting kinases (MNKs) modulate protein translation through the phosphorylation of eukaryotic initiation factor 4E (eIF4E) at serine 209, which is crucial for tumorigenesis but dispensable for normal development. MNKs are implicated in various pathological processes, including inflammation, obesity, cancer, etc. Thus, MNKs are considered as potential drug targets and the development of potent and selective MNK inhibitors is a current research focus.AREAS COVEREDThis review covers inhibitors of MNKs reported in patents published in the online databases of the World Intellectual Property Organization and European Patent Office from 2019 to 2024. This review provides a landscape of available inhibitors, including their chemical structures, activity, and stage of development.EXPERT OPINIONIn recent years, highly potent and selective inhibitors have been discovered and many of them show promising results in several preclinical cancer models. The majority of small-molecule inhibitors developed recently, similarly to the structure of eFT508 and ETC-206. Also, some new skeletons were disclosed and showed novel mechanisms, including non-traditional ATP competition and induced protein degradation by proteolysis targeting chimeras. Ongoing preclinical research and clinical trials will provide us more information on these new compounds and MNKs novel functions beyond cancer.

03 Feb 2025·Clinical Cancer Research

Phase Ib Pharmacodynamic Study of the MNK Inhibitor Tomivosertib (eFT508) Combined With Paclitaxel in Patients With Refractory Metastatic Breast Cancer

Article

Author: del Rincon, Sonia ; Amiri, Mehdi ; Cheng, Grace ; Negri, Gian L. ; Levasseur, Nathalie ; Oo, Htoo Zarni ; Hindmarch, Charles C.T. ; Miller, Wilson H. ; Spera, Gonzalo ; Gelmon, Karen A. ; Pollak, Michael ; Morin, Gregg B. ; Gregorczyk, Kevin ; Ferrario, Cristiano ; Cotechini, Tiziana ; Basiri, Tayebeh ; Sperry, Sam ; Spencer, Sandra E. ; Tse, Veronica W.L. ; Sorensen, Poul H. ; Villareal-Corpuz, Victor ; Gonçalves, Christophe ; Mackey, John ; Sonenberg, Nahum

AbstractPurpose:Preclinical data motivate clinical evaluation of inhibitors of MAPK-interacting kinases 1 and 2 (MNK1/2). We conducted a phase 1b clinical trial to study target engagement and safety of tomivosertib, a MNK1/2 inhibitor, alone and in combination with paclitaxel.Patients and Methods:Eligible patients had metastatic breast cancer resistant to standard-of-care treatments. Biopsies were obtained at baseline and during treatment with tomivosertib, and then tomivosertib was continued with the addition of paclitaxel until disease progression or toxicity. Serum drug levels were measured, and pharmacodynamic endpoints included IHC, proteomics, translatomics, and imaging mass cytometry.Results:Tomivosertib alone and in combination with paclitaxel was well tolerated. There was no pharmacokinetic interaction between the drugs. We observed a clear reduction in phosphorylation of eIF4E at S209, a major substrate of MNK1/2, and identified tomivosertib-induced perturbations in the proteome, translatome, and cellular populations of biopsied metastatic breast cancer tissue.Conclusions:We conclude that tomivosertib effectively inhibits MNK1/2 activity in metastatic breast cancer tissue and that it can safely be combined with paclitaxel in future phase II studies. We demonstrate feasibility of using proteomic profiles, translatomic profiles, and spatial distribution of immune cell infiltrates for clinical pharmacodynamic studies.

14 Jan 2025·ChemPhysChem

Computational Assessment of Clinical Drugs against SARS‐CoV‐2: Foreseeing Molecular Mechanisms and Potent Mpro Inhibitors

Article

Author: Panda, Saroj Kumar ; Sen Gupta, Parth Sarthi ; Kumar Rana, Malay ; Pani, Pratyush ; Mahanandia, Nimai

AbstractThe emergence of new SARS‐CoV‐2 variants of concern (VOC) is a propulsion for accelerated potential therapeutic discovery. SARS‐CoV‐2’s main protease (Mpro), essential for host cell viral replication, is a pre‐eminent druggable protein target. Here, we perform extensive drug re‐profiling of the comprehensive Excelra database, which compiles various under‐trial drug candidates for COVID‐19 treatment. For mechanistic understanding, the most promising screened‐out molecules with targets are subjected to molecular dynamics (MD) simulations. Post‐MD analyses demonstrate Darunavir, Ponatinib, and Tomivosertib forming a stable complex with Mpro, characterized by less fluctuation of Cα atoms, smooth and stable root‐mean‐square deviation (RMSD), and robust contact with the active site residues. Likewise, they all have lower binding free energy with Mpro, demonstrating strong affinity. In free energy landscape profiles, the distances from His41 and Cys145 exhibit a single energy minima basin, implying their preponderance in proximity to Mpro's catalytic dyad. Overall, the computational assessment earmarks promising candidates from the Excelra database, emphasizing on carrying out exhaustive biochemical experiments along with clinical trials. The work lays the foundation for potential therapeutic interventions in treating COVID‐19.

News (Medical) associated with Tomivosertib

07 Nov 2024

·www.prnewswire.com

Tyra Biosciences Reports Third Quarter 2024 Financial Results and Highlights

- Reported positive interim clinical proof-of-concept results for TYRA-300 in mUC from SURF301 Ph1/2 study - - IND cleared for Phase 2 study of TYRA-300 in pediatric achondroplasia (BEACH301) - - Strengthened leadership with appointment of Doug Warner, MD as Chief Medical Officer - - Cash, cash equivalents, and marketable securities of $360.1 million at Q3 2024 - CARLSBAD, Calif., Nov. 7, 2024 /PRNewswire/ -- Tyra Biosciences, Inc. (Nasdaq: TYRA), a clinical-stage biotechnology company focused on developing next-generation precision medicines that target large opportunities in Fibroblast Growth Factor Receptor (FGFR) biology, today reported financial results for the quarter ended September 30, 2024, and highlighted recent corporate progress. "These are exciting times at TYRA. We are very pleased with the interim data reported with TYRA-300 at ENA 2024. TYRA-300 demonstrated impressive anti-tumor activity at dose levels ≥ 90 mg once daily and was generally well-tolerated with infrequent FGFR1 and FGFR2 toxicities that limit the tolerability of pan-FGFR inhibitors. These data provide clinical support that an FGFR3 inhibitor designed to be highly selective can deliver meaningful clinical benefit to heavily pretreated patients with cancer," said Todd Harris, CEO of TYRA. "These results allow us to expand into larger studies for multiple bladder cancer indications, including metastatic urothelial cancer (mUC) and non-muscle invasive bladder cancer (NMIBC), while aiming to achieve best-in-class annualized growth velocity in achondroplasia (ACH). We look forward to initiating the Phase 2 study for ACH in the first quarter of 2025 and submitting an IND for NMIBC by the end of this year." Third Quarter 2024 and Recent Corporate Highlights TYRA-300 Reported Interim Clinical Proof-of-Concept Results from SURF301 Phase 1/2 Study (NCT05544552) in Patients with mUC. In October 2024, TYRA reported interim data with TYRA-300 during a late-breaking oral presentation at the 36th EORTC-NCI-AACR (ENA) Symposium on Molecular Targets and Cancer Therapeutics in Barcelona, Spain. The results included encouraging preliminary anti-tumor activity observed in a heavily pre-treated population: at ≥ 90 mg once daily (QD), 6 out of 11 (54.5%) patients with FGFR3+ mUC achieved a confirmed partial response (PR), with 100% disease control rate and sustained duration of activity; positive safety results were reported across all once-daily (QD) doses, with infrequent FGFR2/FGFR1-associated toxicities. The interim results warrant continued development of TYRA-300 for mUC and the Company is prioritizing QD dosing in SURF301 and future oncology studies. TYRA-300 is currently being evaluated in Part B of SURF301 at potentially therapeutic QD doses in preparation for potential future Phase 2 studies in NMIBC and mUC. Phase 2 IND Submission for NMIBC on Track for Year-End 2024. TYRA plans to expand the clinical development of TYRA-300 into NMIBC to address the unmet needs in this cancer population with an efficacious, orally available therapy. TYRA remains on track to submit an Investigational New Drug (IND) application for a Phase 2 study of TYRA-300 in NMIBC before year-end 2024. IND Clearance Received for Phase 2 Achondroplasia (ACH) Study (BEACH301). In October 2024, TYRA announced that the U.S. Food and Drug Administration (FDA) cleared its IND application for TYRA-300 allowing the company to proceed with a Phase 2 clinical trial of TYRA-300 for children with achondroplasia (BEACH301). The study will be a Phase 2, multicenter, open-label, dose-escalation/dose-expansion study evaluating TYRA-300 in children ages 3 to 10 with achondroplasia with open growth plates. The study will enroll children who are treatment-naïve (Cohort 1) and those who have received prior growth-accelerating therapy (Cohort 2) at multiple sites across the globe. Each of these cohorts is expected to enroll up to 10 participants per dose level (0.125, 0.25, 0.375, 0.50 mg/kg) for up to 12 months. Prior to initiation of Cohorts 1 and 2, the study will enroll a safety sentinel cohort of up to 3 treatment-naïve participants per dose level in children ages 5 to 10. TYRA expects to dose the first child with achondroplasia in BEACH301 in Q1 2025. Peer-Reviewed Manuscript Published in Journal of Medicinal Chemistry. In September 2024, a manuscript titled "Discovery of TYRA-300: First oral selective FGFR3 inhibitor for the treatment of urothelial cancers and achondroplasia" was published in the Journal of Medicinal Chemistry (J. Chem) by the American Chemical Society. The published data provides preclinical evidence that TYRA-300 is a potentially best-in-class, novel precision small molecule designed to be selective for FGFR3 while sparing FGFR1 and 2 isoform toxicities and on-target gatekeeper resistant mutations. These results support the advancement of TYRA-300 in the ongoing SURF301 Phase 1/2 clinical study and the expansion into achondroplasia and hypochondroplasia. TYRA-200 Phase 1 SURF201 Study Continued to Advance. The SURF201 ( Study in Previo Usly treated and Resistant FGFR2+ Cholangiocarcinoma and Other Advanced Solid Tumors) (NCT06160752) continued to advance. The study is a multi-center, open label study designed to evaluate the safety, tolerability, and PK of TYRA-200 and determine the optimal and maximum tolerated dose (MTD) and RP2D, as well as evaluate the preliminary antitumor activity of TYRA-200. TYRA-200 is an investigational, FGFR1/2/3 inhibitor with potency against activating FGFR2 gene alterations and resistance mutations. The SURF201 study is currently enrolling and dosing adults with unresectable locally advanced/metastatic intrahepatic cholangiocarcinoma and other advanced solid tumors with activating FGFR2 gene alterations. TYRA-430 Continued Phase 1 Planning Following IND Clearance. TYRA announced that the FDA cleared its IND to proceed with a Phase 1 clinical study of TYRA-430, an investigational, FGFR4/3-biased inhibitor for FGF19+/FGFR4-driven cancers. The Phase 1 study will be a multicenter, open-label, first-in-human study of TYRA-430 in advanced hepatocellular carcinoma (HCC) and other solid tumors with activating FGF/FGFR pathway aberrations (SURF431). We believe TYRA-430 has the potential to address a significant unmet need in HCC, where there are no approved biomarker-driven, targeted therapies. Corporate Appointed Doug Warner, MD, as Chief Medical Officer (CMO). In September 2024, TYRA announced the appointment of Dr. Warner as CMO, who brings over twenty years of proven clinical development leadership to TYRA having successfully led global development and secured approvals for medicines across oncology and skeletal disease. Prior to TYRA, Dr. Warner held roles of increasing responsibility over 18 years at Amgen where he oversaw clinical development for programs across oncology and bone diseases. This included being an Executive Director and Group Product Area Lead, where Dr. Warner led a team responsible for the development of a portfolio of medicines ranging from those in Phase 1 to those with approved indications, including Vectibix®, XGEVA®, and Prolia®. Most recently, Dr. Warner was Chief Medical Officer for eFFECTOR Therapeutics where he was responsible for overseeing eFFECTOR's clinical pipeline, including its KICKSTART Phase 2b trial of tomivosertib in non-small cell lung cancer, and its Phase 1/2 study of zotatifin in solid tumors. Dr. Warner is co-author of numerous peer-reviewed articles including those in The Lancet, The Lancet Oncology, and The Journal of Clinical Oncology. He received his B.A. from the University of Pennsylvania, his M.D. from the Duke University School of Medicine, and his M.B.A. from the UCLA Anderson School of Management. SNÅP Platform and Pipeline TYRA continued to advance its in-house precision medicine discovery engine, SNÅP, to develop therapies in targeted oncology and genetically defined conditions. Third Quarter 2024 Financial Results Third quarter 2024 net loss was $24.0 million compared to $21.2 million for the same period in 2023. Third quarter 2024 research and development expenses were $22.7 million compared to $19.3 million for the same period in 2023. The increase was driven by increased expenses incurred in connection with our ongoing and planned clinical trials and personnel-related costs, partially offset by decreased drug manufacturing and preclinical costs. Third quarter 2024 general and administrative expenses were $5.9 million compared to $4.7 million for the same period in 2023. The increase was primarily driven by increased personnel-related costs, including stock-based compensation. As of September 30, 2024, TYRA had cash, cash equivalents, and marketable securities of $360.1 million. The Company's current cash, cash equivalents and marketable securities are expected to allow TYRA to execute on its plans through at least 2026. About TYRA-300 TYRA-300 is the Company's lead precision medicine program stemming from its in-house SNÅP platform. TYRA-300 is an investigational, oral, FGFR3-selective inhibitor currently in development for the treatment of cancer and skeletal dysplasias, including achondroplasia and hypochondroplasia. In oncology, TYRA-300 is being evaluated in a multi-center, open label Phase 1/2 clinical study, SURF301 ( Study in Untreated and Resistant FGFR3+ Advanced Solid Tumors) (NCT05544552). The study is designed to determine the optimal and the recommended Phase 2 dose (RP2D) of TYRA-300, as well as to evaluate the preliminary antitumor activity of TYRA-300. Part A of the study included patients with all solid tumors who are FGFR3 +/-, and explored doses of TYRA-300 ranging from 10mg -120mg once-daily (QD). Part A of SURF301 is complete. The Company continues to advance TYRA-300 through dose expansion in Part B, which includes patients with solid tumors who are FGFR3+, to evaluate potentially therapeutic doses in preparation for potential future Phase 2 studies in metastatic urothelial carcinoma (mUC) and non-muscle invasive bladder cancer (NMIBC). In skeletal dysplasia, TYRA-300 has demonstrated positive preclinical results in achondroplasia and hypochondroplasia and TYRA has received IND clearance from the FDA to proceed with its BEACH301 clinical trial in children with achondroplasia. About TYRA-200 TYRA-200 is an investigational, oral, FGFR1/2/3 inhibitor with potency against activating FGFR2 gene alterations and resistance mutations currently in development for the treatment of cancer. TYRA-200 is being evaluated in a multi-center, open label Phase 1 clinical study, SURF201 ( Study in Previo Usly treated and Resistant FGFR2+ Cholangiocarcinoma and Other Advanced Solid Tumors). SURF201 (NCT06160752) was designed to determine the optimal and MTD and the RP2D of TYRA-200, as well as to evaluate the preliminary antitumor activity of TYRA-200. SURF201 is currently enrolling adults with advanced/metastatic intrahepatic cholangiocarcinoma and other advanced solid tumors with activating alterations in FGFR2. About Tyra Biosciences Tyra Biosciences, Inc. (Nasdaq: TYRA) is a clinical-stage biotechnology company focused on developing next-generation precision medicines that target large opportunities in FGFR biology. The Company's in-house precision medicine platform, SNÅP, enables rapid and precise drug design through iterative molecular SNÅPshots that help predict genetic alterations most likely to cause acquired resistance to existing therapies. TYRA's expertise in FGFR biology has created a differentiated pipeline with three clinical-stage programs in targeted oncology and genetically defined conditions. The Company's lead precision medicine stemming from SNÅP, TYRA-300, is a potential first-in-class selective FGFR3 inhibitor that is designed to avoid the toxicities associated with inhibition of FGFR1, FGFR2 and FGFR4, while being agnostic for the FGFR3 gatekeeper mutations. TYRA-300 is in development for the treatment of cancer in the SURF301 Phase 1/2 study and for achondroplasia in the BEACH301 Phase 2 study. TYRA is also developing TYRA-200, an investigational, FGFR1/2/3 inhibitor, in the SURF201 study for metastatic intrahepatic cholangiocarcinoma, and TYRA-430, an investigational FGFR4/3-biased inhibitor for FGF19+/FGFR4-driven cancers. TYRA is based in Carlsbad, CA. For more information about our science, pipeline and people, please visit and engage with us on LinkedIn. Forward-Looking Statements TYRA cautions you that statements contained in this press release regarding matters that are not historical facts are forward-looking statements. The forward-looking statements are based on our current beliefs and expectations and include, but are not limited to: the potential to develop next-generation and potentially best-in-class precision medicines and the potential safety and therapeutic benefits of TYRA-300, TYRA-200, TYRA-430 and other product candidates; the continued evaluation of TYRA-300 through Part B dose escalation in SURF301; the sufficiency of our cash position to support our clinical and operational plans; expected cash runway; the expected timing and phase of clinical development of TYRA-300, TYRA-200, and TYRA-430, including timing of a submission of an IND for TYRA-300 in NMIBC and initiating dosing in BEACH301; the design and goals of BEACH301; and the potential for SNÅP to develop therapies in targeted oncology and genetically defined conditions. Actual results may differ from those set forth in this press release due to the risks and uncertainties inherent in our business, including, without limitation: interim results of a clinical trial are not necessarily indicative of final results and one or more of the clinical outcomes may materially change as patient enrollment continues, following more comprehensive reviews of the data, as follow-up on the outcome of any particular patient continues and as more patient or final data becomes available, including the risk that unconfirmed responses may not ultimately result in confirmed responses to treatment after follow-up evaluations; the potential for proof-of-concept results to fail to result in successful subsequent development of TYRA-300; we are early in our development efforts of testing TYRA-300 and TYRA-200 for oncology in clinical trials and the approach we are taking to discover and develop drugs based on our SNÅP platform is novel and unproven and it may never lead to product candidates that are successful in clinical development or approved products of commercial value; potential delays in the commencement, enrollment, data readouts and completion of preclinical studies and clinical trials; results from preclinical studies or early clinical trials not necessarily being predictive of future results; later developments with the FDA may be inconsistent with prior feedback from the FDA, including with respect to the proposed initiation and design of our BEACH301 study; our dependence on third parties in connection with manufacturing, research and preclinical testing; we may expend our limited resources to pursue a particular product candidate and/or indication and fail to capitalize on product candidates or indications with greater development or commercial potential; acceptance by the FDA of INDs or of similar regulatory submissions by comparable foreign regulatory authorities for the conduct of clinical trials of TYRA-300 in pediatric achondroplasia and hypochondroplasia; an accelerated development or approval pathway may not be available for TYRA-300 or other product candidates and any such pathway may not lead to a faster development process; later developments with the FDA may be inconsistent with the minutes from our prior meetings, including with respect to the proposed design of our planned Phase 2 study of TYRA-300 in ACH; unexpected adverse side effects or inadequate efficacy of our product candidates that may limit their development, regulatory approval, and/or commercialization; the potential for our programs and prospects to be negatively impacted by developments relating to our competitors, including the results of studies or regulatory determinations relating to our competitors; unfavorable results from preclinical studies; we may not realize the benefits associated with Orphan Drug Designation, including that orphan drug exclusivity may not effectively protect a product from competition and that such exclusivity may not be maintained, or from the Rare Pediatric Disease Designation, including receipt of a Priority Review Voucher or any value therefrom; regulatory developments in the United States and foreign countries; our ability to obtain and maintain intellectual property protection for our product candidates and proprietary technologies; we may use our capital resources sooner than we expect; unstable market and economic conditions and military conflict may adversely affect our business and financial condition and the broader economy and biotechnology industry; and other risks described in our prior filings with the Securities and Exchange Commission (SEC), including under the heading "Risk Factors" in our annual report on Form 10-K and any subsequent filings with the SEC. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and we undertake no obligation to update such statements to reflect events that occur or circumstances that exist after the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement, which is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Contact: Amy Conrad [email protected] SOURCE Tyra Biosciences WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Phase 1Phase 2Clinical ResultINDExecutive Change

24 Jun 2024

·www.fiercebiotech.com

The end of eFFECTOR Therapeutics: Oncology biotech winds down after midstage fail

Part of the next steps include looking for strategic alternatives for eFFECTOR’s development programs. It’s the end of an era—eFFECTOR Therapeutics’ era to be exact. The oncology biotech has laid off staff as it plans to wind down, according to a June 24 company release. This includes eFFECTOR CEO Stephen Worland, Ph.D.; Chief Financial Officer Michael Byrnes; and Chief Medical Officer Douglas Warner, M.D., who all stopped serving in their positions at the end of last week. The company expects to spend about $600,000 by June 30 in one-time charges and cash expenditures tied to the workforce reduction, according to Securities and Exchange Commission documents. In the meantime, the board of directors has tapped Craig Jalbert to lead as eFFECTOR’s CEO, president, treasurer, secretary and sole board member. Jalbert is a principal from the accounting firm Verdolino & Lowey, P.C., and has more than three decades of experience helping companies wind down. Part of the next steps include looking for strategic alternatives for eFFECTOR’s development programs. The biotech’s lead asset is zotatifin, a selective eIF4A inhibitor being tested out in several mid-stage trials for solid tumors. In April, the company's other wholly-owned asset, tomivosertib, failed to improve progression-free survival in a phase 2b trial of patients with non-small cell lung cancer (NSCLC). Based on all the data available in the primary analysis, the company said it didn't see an obvious path forward for continuing development of the asset in frontline NSCLC. eFFECTOR also had a partnership with Big Pharma Pfizer for a preclinical asset dubbed eIF4Ei, which is also designed to tackle solid tumors. The $507 million biobucks deal was struck back in 2019 when Pfizer paid out $15 million up front in an exclusive licensing agreement to develop small-molecule inhibitors of eukaryotic initiation factor 4E (eIF4E) with eFFECTOR. The biotech was founded in 2012 based on research from the University of California, San Francisco labs of Davide Ruggero, Ph.D., and Kevan Shokat, Ph.D. eFFECTOR plans to ask to be delisted from the Nasdaq. Since announcing the planned shuttering, the biotech’s stock plummeted 77% from $1.17 per share at market close Friday to 29 cents this morning at opening.

Phase 2License out/inExecutive ChangePhase 1

20 May 2024

·www.globenewswire.com

eFFECTOR Therapeutics to Collaborate with the Dana-Farber Cancer Institute on an Investigator-Sponsored Phase 2 Clinical Trial Evaluating Zotatifin as Combination Treatment in ER+ Endometrial Cancer and in Low Grade Serous Ovarian Cancer

SOLANA BEACH, Calif. and REDWOOD CITY, Calif., May 20, 2024 (GLOBE NEWSWIRE) -- eFFECTOR Therapeutics, Inc. (NASDAQ: EFTR), a leader in the development of selective translation regulator inhibitors (STRIs) for the treatment of cancer, today announced a collaboration to conduct an investigator-sponsored trial (IST) evaluating zotatifin in combination with abemaciclib and letrozole in patients with estrogen receptor-positive (ER+) endometrial cancer and low grade serous ovarian cancer at the Dana-Farber Cancer Institute (DFCI) under the direction of Panagiotis Konstantinopoulos, M.D., Ph.D., Director of Translational Research and attending oncologist in the Division of Gynecologic Oncology at DFCI, and an Associate Professor of Medicine at Harvard Medical School. “Endometrial cancer is the most prevalent cancer affecting the female reproductive organs in the United States,” said Dr. Konstantinopoulos. “While early detection offers hope for successful treatment, patients with recurrent or metastatic disease have limited treatment options. Recent studies of the abemaciclib and letrozole combo in ER+ endometrial cancer patients have shown promising activity, however, most patients either fail to respond or eventually develop resistance to CDK4/6 inhibition, a critical aspect of treatment. Similarly, low grade serous ovarian cancer has shown sensitivity to combined treatment with aromatase inhibitors and CDK4/6 inhibition, but responding patients eventually develop disease progression. By targeting eIF4A, which subsequently downregulates the key factors implicated in CDK4/6 inhibition resistance, we believe that integrating zotatifin with abemaciclib and letrozole treatment regimen represents a compelling strategy for combating recurrent endometrial cancer and low grade serous ovarian cancer.” Doug Warner, M.D., chief medical officer of eFFECTOR Therapeutics added, “We are thrilled to embark on this investigator-sponsored Phase 2 trial in collaboration with Dr. Konstantinopoulos and his team at the DFCI. This trial represents a significant step forward in our collective efforts to address the complexities of endometrial cancer and low grade serous ovarian cancer. By exploring the potential of zotatifin as a combination treatment and its unique mechanism of action, we aim to redefine the treatment landscape and improve outcomes for these patients. With this comprehensive approach which simultaneously targets tumor cell cycle progression while reducing estrogen levels, we hope to overcome resistance mechanisms and enhance treatment efficacy which we believe could be applied in various malignancies beyond breast and endometrial cancers. In parallel, we continue to advance development of zotatifin in ER+ metastatic breast cancer and anticipate determination of the Phase 2 dose (RP2D) of zotatifin in combination with fulvestrant and abemaciclib, in the second half of 2024.” About Zotatifin Zotatifin is a potent and sequence-selective small molecule inhibitor of the RNA helicase eIF4A that is designed to suppress the overproduction of cell cycle proteins and oncogenes, including Cyclins D and E, CDKs 4 and 6, ERα, KRAS, HER2, and other RTKs. Zotatifin is currently being evaluated in a Phase 2a expansion cohort in combination with fulvestrant and abemaciclib in ER+ breast cancer. Efficacy data presented at 2023 ASCO and SABCS showed a 26% response rate and mPFS of 7.4 months as a triplet in heavily pretreated patients. About eFFECTOR Therapeutics eFFECTOR is a clinical-stage biopharmaceutical company pioneering the development of a new class of oncology drugs referred to as STRIs. eFFECTOR’s STRI product candidates target the eIF4F complex and its activating kinase, mitogen-activated protein kinase interacting kinase (MNK). The eIF4F complex is a central node where two of the most frequently mutated signaling pathways in cancer, the PI3K-AKT and RAS-MEK pathways, converge to activate the translation of select mRNA into proteins that are frequent culprits in key disease-driving processes. Each of eFFECTOR’s product candidates is designed to act on a single protein that drives the expression of a network of functionally related proteins, including oncoproteins and immunosuppressive proteins in T cells, that together control tumor growth, survival, and immune evasion. Zotatifin, eFFECTOR’s inhibitor of eIF4A, is currently being evaluated in a Phase 2a expansion cohort in combination with fulvestrant and abemaciclib in ER+ breast cancer and in Phase 2 IST in combination with abemaciclib and letrozole in ER+ endometrial cancer. Tomivosertib, eFFECTOR’s MNK inhibitor, is currently being evaluated in an investigator-sponsored trial in AML. eFFECTOR has a global collaboration with Pfizer to develop inhibitors of a third target, eIF4E. Forward-Looking StatementseFFECTOR cautions you that statements contained in this press release regarding matters that are not historical facts are forward-looking statements. The forward-looking statements are based on our current beliefs and expectations and include, but are not limited to: the future clinical development of our product candidates, including expectations on enrollment and the timing of reporting data from ongoing clinical trials; the potential therapeutic benefits of our product candidates; and the timing and potential benefits of the IST evaluating zotatifin in combination with abemaciclib and letrozole in patients with ER+ endometrial cancer and low grade serous ovarian cancer. Actual results may differ from those set forth in this press release due to the risks and uncertainties inherent in our business, including, without limitation: potential delays in the commencement, enrollment and completion of clinical trials, including the IST conducted by DFCI; the success of our clinical trials and preclinical studies for our product candidates is uncertain; we are dependent on DFCI to conduct the IST trial and we may not realize any benefits from the collaboration with DFCI; our dependence on third parties in connection with product manufacturing, research and preclinical and clinical testing; the results of preclinical studies and early clinical trials are not necessarily predictive of future results; regulatory developments in the United States and foreign countries; unexpected adverse side effects or inadequate efficacy of our product candidates that may limit their development, regulatory approval and/or commercialization, or may result in recalls or product liability claims; and other risks described in our prior filings with the Securities and Exchange Commission. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and we undertake no obligation to update such statements to reflect events that occur or circumstances that exist after the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement, which is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Contacts: Investors: Christopher M. CalabreseManaging DirectorLifeSci Advisors917-680-5608ccalabrese@lifesciadvisors.com Kevin GardnerManaging DirectorLifeSci Advisors617-283-2856kgardner@lifesciadvisors.com Media: Michael Fitzhugh Vice President, Chief of Media StrategyLifeSci Communicationsmfitzhugh@lifescicomms.com

Phase 2Clinical ResultPhase 1

100 Deals associated with Tomivosertib

External Link

KEGG	Wiki	ATC	Drug Bank
D11452	-	-	DB15219

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Breast Cancer	Phase 2	-	Merck Serono SA	-
Breast Cancer	Phase 2	-	Pfizer Inc.	-
Colorectal Cancer	Phase 2	-	Pfizer Inc.	-
Colorectal Cancer	Phase 2	-	Merck Serono SA	-
Hepatocellular Carcinoma	Phase 2	-	Merck Serono SA	-
Hepatocellular Carcinoma	Phase 2	-	Pfizer Inc.	-
Lymphoma	Phase 2	-	Pfizer Inc.	-
Lymphoma	Phase 2	-	Merck Serono SA	-
Diffuse Large B-Cell Lymphoma	Preclinical	United States	eFFECTOR Therapeutics Operations, Inc.	28 Sep 2016
Advanced Malignant Solid Neoplasm	Preclinical	United States	eFFECTOR Therapeutics Operations, Inc.	03 Dec 2015

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03690141 (CTgov)	Phase 2	Castration-Resistant Prostatic Cancer	16	eFT508	jyzurjadwg(djaptnpyyb) = lutkjfhpmn bgiurrwybj (zydjchxqks, fiqaeqfodk - xfzmecaizn)	-	21 Jun 2024
NCT04622007 (KICKSTART, Corporate Publications) Manual	Phase 2	Non-Small Cell Lung Cancer First line PD-L1 ≥50%	-	tomivosertib+pembrolizumab	(lyrpbjshcr) = hayqbluqga qglhlchbcc (ausmufnbgx ) Not Met View more	Negative	04 Apr 2024
				Placebo+pembrolizumab	(lyrpbjshcr) = cqifhsmxia qglhlchbcc (ausmufnbgx ) Not Met View more
NCT04261218 (AACR2022)	Phase 1	Metastatic breast cancer	14	Tomivosertib	ftjjubjyjm(oxhxlymbqa) = mawyrenhhm uleatgonry (ngwvyubyvh, +/ - 40)	-	15 Jun 2022
				Paclitaxel	exhsvauqbx(nmjtietfzb) = dgmpqifvyv mtflvaiddv (sedgoinmvw, +/ - 220)
NCT03258398 (ASCO 12019 \| ASCO 22019) Manual	Phase 2	Metastatic Microsatellite Stable Colorectal Carcinoma Third line Microsatellite Stable (MSS)	52	avelumab+tomivosertib	(cxkqhqksgk) = lecimnlkxt atyhxjlcxe (ckfskuqvkh ) View more	Positive	31 May 2019
				avelumab+tomivosertib	(etxwlrbjxo) = pgrxhvhaci ibufpbzflk (tzpybslark )
NCT02605083 (ASCO2017)	Phase 1	HR-positive/HER2-low Solid Tumors	28	eFT508	qmfoufzbad(cncosiglba) = one pt with reversible Gr3 AST/ALT elevation gdmdrkdcrd (jlxptgedvu ) View more	-	30 May 2017

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