A Phase 1b/2 Open-Label Study of the Efficacy and Safety of Etigilimab (MPH313) Administered in Combination With Nivolumab to Subjects With Locally Advanced or Metastatic Solid Tumors (ACTIVATE)

This is an open-label, phase 1b/2, multicenter study designed to evaluate the efficacy, safety, tolerability, PK, and pharmacodynamics of etigilimab in combination with nivolumab in subjects with locally advanced or metastatic solid tumors. Subjects will be assigned to receive etigilimab (every 2 weeks) in combination with nivolumab (240 mg every 2 weeks).

Start Date23 Mar 2021

Sponsor / Collaborator

Mereo BioPharma Group Plc

[+1]

NCT03119428 / TerminatedPhase 1

A Phase 1a/b Open-Label, Dose-Escalation Study of the Safety and Pharmacokinetics of OMP-313M32 Administered as a Single Agent or in Combination With Nivolumab to Subjects With Locally Advanced or Metastatic Solid Tumors

The purpose of this study is to evaluate the safety and tolerability of OMP-31M32 as a single agent or in combination with nivolumab. OMP-313M32 is an experimental anti-TIGIT antibody that was developed to block TIGIT from binding PVR allowing the body's T-cells to destroy cancer cells.

Start Date02 May 2017

Sponsor / Collaborator

Mereo BioPharma 5, Inc.

NCT05026606 / Active, not recruitingPhase 2IIT

EON: A Single-Arm Phase II Study of Etigilimab (OMP-313M32) in Combination With Checkpoint Inhibition (Nivolumab) in Patients With Platinum-Resistant, Recurrent Epithelial Ovarian Cancer

This phase II trial the side effects and possible benefits of etigilimab and nivolumab in treating patients with platinum-resistant clear cell ovarian, primary peritoneal, or fallopian tube cancer that has come back (recurrent). Immunotherapy with monoclonal antibodies, such as etigilimab and nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. The goal of this clinical trial is to learn if adding etigilimab to nivolumab therapy can help to control clear cell ovarian, fallopian tube, and primary peritoneal cancers that are resistant to platinum-based therapy.

Start Date-

Sponsor / Collaborator

The University of Texas MD Anderson Cancer Center

100 Clinical Results associated with Etigilimab

100 Translational Medicine associated with Etigilimab

100 Patents (Medical) associated with Etigilimab

Literatures (Medical) associated with Etigilimab

01 Oct 2023·Journal for immunotherapy of cancer

AdvanTIG-105: a phase I dose escalation study of the anti-TIGIT monoclonal antibody ociperlimab in combination with tislelizumab in patients with advanced solid tumors

Article

Author: Rizwan, Ahsan ; Frentzas, Sophia ; Budha, Nageshwar ; Tan, Wei ; Zheng, Hao ; Meniawy, Tarek ; Kao, Steven ; de la Hoz Pedroza, Luz ; Gao, Rang

Background:

Ociperlimab, a novel, humanized monoclonal antibody (mAb), binds to T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) with high affinity and specificity. Tislelizumab is an anti-programmed cell death protein 1 mAb. We report results from a phase I, first-in-human, dose escalation study evaluating the safety, pharmacokinetics (PK), and preliminary antitumor activity of ociperlimab plus tislelizumab in patients with advanced solid tumors.

Methods:

Eligible patients previously treated with standard systemic therapy, or for whom treatment was not available or tolerated, received ociperlimab intravenously on Cycle (C) 1 Day (D) 1 and tislelizumab 200 mg intravenously on C1 D8. If tolerated, patients received ociperlimab plus tislelizumab 200 mg sequentially on D29 and every 3 weeks (Q3W) thereafter until discontinuation. Dose escalation for ociperlimab was planned with four dose levels (50 mg, 150 mg, 450 mg, and 900 mg) according to a 3+3 design. An additional dose level of ociperlimab 1800 mg was also assessed. Primary endpoints were safety, determination of the maximum tolerated (or administered) dose, and the recommended phase II dose (RP2D). Secondary endpoints included overall response rate (ORR), duration of response (DoR), disease control rate (DCR) (Response Evaluation Criteria in Solid Tumors version 1.1), PK, and biomarker analysis.

Results:

At data cut-off (September 29, 2022), 32 patients had received ≥1 dose of ociperlimab plus tislelizumab 200 mg Q3W. The maximum administered dose was ociperlimab 1800 mg plus tislelizumab 200 mg Q3W. The median age of enrolled patients was 59.5 years (range: 31–79). Most patients (96.9%) experienced ≥1 treatment-emergent adverse event (TEAE); 62.5% of patients experienced ≥grade 3 TEAEs and 50.0% of patients experienced serious TEAEs. No dose limiting toxicity events were reported. The maximum tolerated dose was not reached. The RP2D was ociperlimab 900 mg plus tislelizumab 200 mg Q3W. Overall, ORR was 10.0%, median DoR was 3.6 months, and DCR was 50.0%.

Conclusions:

Ociperlimab plus tislelizumab was well tolerated in patients with advanced solid tumors, and preliminary antitumor activity was observed with 450 mg, 900 mg, and 1800 mg ociperlimab. Phase II/III trials of ociperlimab 900 mg plus tislelizumab 200 mg Q3W are underway in a range of solid tumors.

Trial registration number:

NCT04047862.

11 May 2023·International journal of molecular sciences

Study on the Effect of EZH2 Inhibitor Combined with TIGIT Monoclonal Antibody against Multiple Myeloma Cells.

Article

Author: Liu, Hui ; Liu, Zhaoyun ; Yang, Chun ; Wang, Hao ; Shen, Hongli ; Fu, Rong ; Jia, Yue

EZH2, a member of the polycomb repressive complex 2, induces trimethylation of the downstream gene at the histone three lysine 27 (H3K27me3) position to inhibit tumor cell proliferation. Here, we showed that the apoptosis rate and apoptotic protein expression increased after EZH2 inhibition, whereas key molecules of the NF-κB signaling pathway and the downstream target genes were inhibited. Additionally, the expression of CD155, a TIGIT high-affinity ligand in multiple myeloma (MM) cells, was decreased by the mTOR signaling pathway. Furthermore, the combination of EZH2 inhibitor and TIGIT monoclonal antibody blockade enhanced the anti-tumor effect of natural killer cells. In summary, the EZH2 inhibitor not only plays an anti-tumor role as an epigenetic drug, but also enhances the anti-tumor effect of the TIGIT monoclonal antibody by affecting the TIGIT-CD155 axis between NK cells and MM cells, thus providing new ideas and theoretical basis for the treatment of MM patients.

09 May 2023·Communications biology

Anti-human-TIGIT agonistic antibody ameliorates autoimmune diseases by inhibiting Tfh and Tph cells and enhancing Treg cells.

Article

Author: Takeshita, Masaru ; Kouro, Taku ; Kaneko, Yuko ; Takeuchi, Tsutomu ; Iizuka, Mana ; Kassai, Yoshiaki ; Ota, Yuichiro ; Yamane, Humitsugu ; Hashikami, Kentarou ; Suzuki, Katsuya ; Yoshimura, Akihiko ; Koga, Keiko ; Kojima, Marenori ; Yoshihara, Tomoki ; Adachi, Ryutaro ; Ohyagi, Masaki ; Morita, Rimpei ; Yoshimoto, Keiko

T cells play important roles in autoimmune diseases, but it remains unclear how to optimally manipulate them. We focused on the T cell immunoreceptor with Ig and ITIM domains (TIGIT), a coinhibitory molecule that regulates and is expressed in T cells. In autoimmune diseases, the association between TIGIT-expressing cells and pathogenesis and the function of human-TIGIT (hu-TIGIT) signalling modification have not been fully elucidated. Here we generated anti-hu-TIGIT agonistic monoclonal antibodies (mAbs) and generated hu-TIGIT knock-in mice to accurately evaluate the efficacy of mAb function. Our mAb suppressed the activation of CD4⁺ T cells, especially follicular helper T and peripheral helper T cells that highly expressed TIGIT, and enhanced the suppressive function of naïve regulatory T cells. These results indicate that our mAb has advantages in restoring the imbalance of T cells that are activated in autoimmune diseases and suggest potential clinical applications for anti-hu-TIGIT agonistic mAbs as therapeutic agents.

News (Medical) associated with Etigilimab

12 Nov 2024

·www.globenewswire.com

Mereo BioPharma Reports Third Quarter 2024 Financial Results and Provides Corporate Update

Setrusumab receives Breakthrough Therapy designation from the FDA Cash of $80.5 million as of September 30, 2024, expected to fund operations into 2027 LONDON, Nov. 12, 2024 (GLOBE NEWSWIRE) -- Mereo BioPharma Group plc (NASDAQ: MREO) (“Mereo” or the “Company”), a clinical-stage biopharmaceutical company focused on rare diseases, today announced its financial results for the third quarter ended September 30, 2024, and provided an update on recent corporate highlights. The Company reported cash and cash equivalents of $80.5 million as of September 30, 2024, which the Company believes will provide runway into 2027, through multiple key inflection points. “The Phase 3 program for setrusumab, led by our partners at Ultragenyx, continues to progress according to plan and we look forward to reporting the topline data during 2025,” said Dr. Denise Scots-Knight, Chief Executive Officer of Mereo. “The recent receipt of Breakthrough Therapy designation from the U.S. FDA follows on from the PRIME designation we obtained in Europe. This reinforces the high unmet medical need for treatments for individuals affected by osteogenesis imperfecta (OI) who currently have no approved therapies, and the potential of setrusumab. Our pre-commercial efforts in our key European markets are progressing well, including the discussions with the HTAs and payors through EUNetHA and scientific advice in the individual countries. We continue to engage in discussions with multiple potential partners regarding the development and commercialization of alvelestat for AATD lung disease. We remain on track for alvelestat to be Phase 3-ready around the end of the year, further solidifying our commitment to bringing innovative treatments to individuals with rare diseases.” Third Quarter 2024 Highlights, Recent Developments and Anticipated Milestones Setrusumab (UX143) Our partner, Ultragenyx Pharmaceutical Inc., received Breakthrough Therapy Designation from the U.S. Food and Drug Administration (FDA) for setrusumab (UX143) as a treatment to reduce the risk of fracture associated with osteogenesis imperfecta (OI) Type I, III, or IV in patients 2 years of age and older. The FDA’s decision was based on preliminary clinical evidence including the positive 14-month results from the Phase 2 portion of the Orbit study, which demonstrated a rapid and clinically meaningful decrease in fracture rate in patients, and from the completed Phase 2b ASTEROID study. Led by Ultragenyx, the Companies are actively advancing the Phase 3 Orbit and Cosmic studies of setrusumab in OI.The 14-month data from the Phase 2/3 Orbit study were presented by Ultragenyx in a late-breaking oral presentation at the American Society for Bone and Mineral Research (ASBMR) 2024 Annual Meeting.A further paper from SATURN (Systematic Accumulation of Treatment practices and Utilization, Real world evidence, and Natural history data for OI), has been published. This is part of the Company’s pre-launch activities designed to generate additional evidence to support coverage, pricing and reimbursement decisions across Europe. Alvelestat (MPH-966) Following the FDA feedback on the detailed Phase 3 package, including the study protocol and the initial validation work on SGRQ in AATD, the Company continues to expect that alvelestat will be Phase 3 ready around the end of 2024.The Company remains in discussions with several potential partners regarding the development and commercialization of alvelestat for AATD. Third Quarter 2024 Financial Results Total research and development (R&D) expenses decreased by $0.4 million, or 12%, from $3.6 million in the third quarter of 2023 to $3.2 million in the third quarter of 2024. The decrease was primarily due to reductions in R&D expenses of $0.6 million and $0.4 million for etigilimab and alvelestat, respectively, partially offset by an increase of $0.4 million for setrusumab. The reduction in program expenses for etigilimab was primarily due to the winding down and completion during 2023 of the open label Phase 1b/2 basket study in combination with an anti-PD-1 in a range of tumor types. The reduction in the program expenses for alvelestat primarily relates to lower levels of preparatory activity undertaken in respect of the Phase 3 study in the three months ended September 30, 2024 compared to 2023, particularly including manufacturing and drug formulation activities and regulatory interactions. The increase in program expenses for setrusumab was driven by additional activities in Europe and resources for input into development, regulatory and manufacturing plans with our partner, Ultragenyx, as the global development program is funded by Ultragenyx pursuant to our license and collaboration agreement. General and administrative (G&A) expenses increased by $0.5 million, or 9%, from $5.7 million in the third quarter of 2023 to $6.2 million in the third quarter of 2024. The increase primarily reflects $0.2 million higher pre-commercial activities to lay the foundation for the commercial launch of setrusumab in Europe, including activities to support pricing and reimbursement by HTA authorities and payor decision-makers in Europe. The remaining increase represents increases in various corporate expenses. Net loss for the third quarter of 2024 was $15.0 million, compared to $6.5 million during the third quarter of 2023. The $9.2 million increase in net loss was driven primarily by a net foreign exchange loss of $6.4 million for the third quarter of 2024, compared to a gain of $2.5 million for the third quarter of 2023. This change primarily reflects a weakening of the U.S. dollar when translating U.S. dollar balances into our functional currency of pound sterling in the third quarter of 2024 and higher U.S. dollar balances. As of September 30, 2024, the Company had cash and cash equivalents of $80.5 million, compared to $57.4 million as of December 31, 2023. This includes net proceeds of the $50 million underwritten registered direct offering priced at-the-market on June 14, 2024. The Company expects, based on current operational plans, that its existing cash and cash equivalents balance will enable it to fund its currently committed clinical trials, operating expenses including pre-commercial activities for setrusumab, and capital expenditure requirements into 2027. This guidance does not include any potential upfront payments associated with a partnership for alvelestat or business development activity around any of the Company’s non-core programs. Total ordinary shares issued as of September 30, 2024, were 773,672,299. Total ADS equivalents as of September 30, 2024, were 154,734,459, with each ADS representing five ordinary shares of the Company. About Mereo BioPharma Mereo BioPharma is a biopharmaceutical company focused on the development of innovative therapeutics for rare diseases. The Company has two rare disease product candidates, setrusumab for the treatment of osteogenesis imperfecta (OI) and alvelestat primarily for the treatment of severe alpha-1 antitrypsin deficiency-associated lung disease (AATD-LD). The Company’s partner, Ultragenyx Pharmaceutical, Inc., has completed enrollment in the Phase 3 portion of a pivotal Phase 2/3 pediatric study in young adults (5 to 25 years old) for setrusumab in OI and in the Phase 3 study in pediatric patients (2 to <7 years old) in the first half of 2024. The partnership with Ultragenyx includes potential additional milestone payments of up to $245 million and royalties to Mereo on commercial sales in Ultragenyx territories. Mereo has retained EU and UK commercial rights and will pay Ultragenyx royalties on commercial sales in those territories. Setrusumab has received orphan designation for osteogenesis imperfecta from the EMA and FDA, PRIME designation from the EMA, and Breakthrough Therapy designation and pediatric disease designation from the FDA. Alvelestat has received U.S. Orphan Drug Designation for the treatment of AATD and Fast Track designation from the FDA. Following results from ASTRAEUS and ATALANTa in AATD-lung disease, the Company has aligned with the FDA and the EMA on the primary endpoints for a Phase 3 pivotal study which if successful could enable full approval in both the U.S. and Europe. In addition to the rare disease programs, Mereo has two oncology product candidates in clinical development. Etigilimab (anti-TIGIT) has completed a Phase 1b/2 basket study evaluating its safety and efficacy in combination with an anti-PD-1 in a range of tumor types and is an ongoing Phase 1b/2 investigator led study at the MD Anderson Cancer Center in clear cell ovarian cancer; Navicixizumab, for the treatment of late line ovarian cancer, has completed a Phase 1 study and has been partnered with Feng Biosciences Inc. in a global licensing agreement that includes milestone payments and royalties. Mereo has entered into an exclusive global license agreement with ReproNovo SA for the development and commercialization of leflutrozole, a non-steroidal aromatase inhibitor. Under the terms of the agreement, ReproNovo, a reproductive medicine company, is responsible for all future development and commercialization of leflutrozole. Forward-Looking Statements This press release contains “forward-looking statements” that involve substantial risks and uncertainties. All statements other than statements of historical fact contained herein are forward-looking statements within the meaning of Section 27A of the United States Securities Act of 1933, as amended, and Section 21E of the United States Securities Exchange Act of 1934, as amended. Forward-looking statements usually relate to future events and anticipated revenues, earnings, cash flows or other aspects of our operations or operating results. Forward-looking statements are often identified by the words “believe,” “expect,” “anticipate,” “plan,” “intend,” “foresee,” “should,” “would,” “could,” “may,” “estimate,” “outlook” and similar expressions, including the negative thereof. The absence of these words, however, does not mean that the statements are not forward-looking. These forward-looking statements are based on the Company’s current expectations, beliefs and assumptions concerning future developments and business conditions and their potential effect on the Company. While management believes that these forward-looking statements are reasonable as and when made, there can be no assurance that future developments affecting the Company will be those that it anticipates.All of the Company’s forward-looking statements involve known and unknown risks and uncertainties some of which are significant or beyond its control and assumptions that could cause actual results to differ materially from the Company’s historical experience and its present expectations or projections. Such risks and uncertainties include, among others, the uncertainties inherent in the clinical development process; the Company’s reliance on third parties to conduct and provide funding for its clinical trials; the Company’s dependence on enrollment of patients in its clinical trials; and the Company’s dependence on its key executives. You should carefully consider the foregoing factors and the other risks and uncertainties that affect the Company’s business, including those described in the “Risk Factors” section of its Annual Report on Form 10-K, as well as discussions of potential risks, uncertainties, and other important factors in the Company’s subsequent filings with the Securities and Exchange Commission. The Company wishes to caution you not to place undue reliance on any forward-looking statements, which speak only as of the date hereof. The Company undertakes no obligation to publicly update or revise any of our forward-looking statements after the date they are made, whether as a result of new information, future events or otherwise, except to the extent required by law. Mereo BioPharma Contacts: Mereo +44 (0)333 023 7300Denise Scots-Knight, Chief Executive Officer Christine Fox, Chief Financial Officer Burns McClellan (Investor Relations Adviser to Mereo) +01 646 930 4406Lee Roth Investors investors@mereobiopharma.com MEREO BIOPHARMA GROUP PLCCONDENSED CONSOLIDATED BALANCE SHEETS(In thousands, except share and per share data)(Unaudited) September 30, December 31, 2024 2023 Assets Current assets: Cash and cash equivalents $80,522 $57,421 Prepaid expenses and other current assets 3,830 5,156 Research and development incentives receivables 2,371 1,183 Total current assets 86,723 63,760 Property and equipment, net 315 405 Operating lease right-of-use assets, net 909 1,245 Intangible assets, net 799 1,089 Total assets $88,746 $66,499 Liabilities Current liabilities: Accounts payable $1,748 $2,346 Accrued expenses 3,529 5,467 Convertible loan notes – current 5,551 — Operating lease liabilities – current 736 652 Other current liabilities 2,644 1,021 Total current liabilities 14,208 9,486 Convertible loan notes – non-current — 4,394 Warrant liabilities – non-current 1,040 412 Operating lease liabilities – non-current 394 906 Other non-current liabilities 568 764 Total liabilities $16,210 $15,962 Commitments and contingencies (Note 16) Shareholders’ Equity Ordinary shares, par value £0.003 per share; 773,672,299 shares issued at September 30, 2024 (December 31, 2023: 701,217,089). 3,051 2,775 Treasury shares — (1,230)Additional paid-in capital 536,426 486,107 Accumulated deficit (455,837) (419,630)Accumulated other comprehensive loss (11,104) (17,485)Total shareholders’ equity 72,536 50,537 Total liabilities and shareholders’ equity $88,746 $66,499 MEREO BIOPHARMA GROUP PLCCONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS(In thousands, except share and per share amounts)(Unaudited) Three Months EndedSeptember 30, Nine Months EndedSeptember 30, 2024 2023 2024 2023 Revenue $— $— $— $9,000 Operating expenses: Cost of revenue — 235 — (2,847)Research and development (3,170) (3,594) (12,109) (12,614)General and administrative (6,203) (5,708) (19,980) (14,827)Loss from operations (9,373) (9,067) (32,089) (21,288)Other income/(expenses) Interest income 983 689 2,160 1,368 Interest expense (353) (700) (995) (2,528)Changes in the fair value of warrants (59) — (576) 440 Foreign currency transaction (loss)/gain, net (6,425) 2,465 (5,780) 455 Other expenses, net — — — (6)Benefit from research and development tax credit 226 82 1,073 1,202 Net loss before income tax (15,001) (6,531) (36,207) (20,357)Income tax benefit — — — — Net loss $(15,001) $(6,531) $(36,207) $(20,357) Loss per share – basic and diluted $(0.02) $(0.01) $(0.05) $(0.03)Weighted average shares outstanding – basic and diluted 770,146,589 684,974,190 727,808,860 645,997,203 Net loss $(15,001) $(6,531) $(36,207) $(20,357)Other comprehensive income/(loss) – Foreign currency translation adjustments, net of tax 7,174 (3,579) 6,381 99 Total comprehensive loss $(7,827) $(10,110) $(29,826) $(20,258)

Breakthrough TherapyPhase 3Clinical ResultFast TrackLicense out/in

12 Nov 2024

·www.globenewswire.com

iTeos Reports Third Quarter 2024 Financial Results and Provides Business Updates

- EMA granted clearance to advance belrestotug 400mg + dostarlimab as recommended Phase 3 dose and activate GALAXIES Lung-301 clinical sites in the EU- Interim data from inupadenant Phase 2 A2A-005 in 2L NSCLC at ESMO-IO- Completed enrollment of EOS-984 Phase 1 monotherapy dose escalation and initiated dosing of EOS-984 + pembrolizumab combination- Pro forma cash and investment balance of $683.9 million as of September 30, 2024 expected to provide runway through 2027 across a number of impactful portfolio milestones WATERTOWN, Mass. and GOSSELIES, Belgium, Nov. 12, 2024 (GLOBE NEWSWIRE) -- iTeos Therapeutics, Inc. (Nasdaq: ITOS), a clinical-stage biopharmaceutical company pioneering the discovery and development of a new generation of immuno-oncology therapeutics for patients, today reported financial results for the third quarter ended September 30, 2024 and provided a business update. “The third quarter represented a period of strong clinical and operational execution across the pipeline for iTeos. As we continue our global rollout for GALAXIES Lung-301, we were delighted to recently dose the first patient in the EU after receiving clearance from the EMA to advance belrestotug 400mg plus dostarlimab. For our adenosine assets, we are pleased to announce three inupadenant presentations at ESMO-IO in December, including dose escalation data from inupadenant’s Phase 2 trial and two poster presentations on EOS-984. Furthermore, the EOS-984 Phase 1 trial has continued to enroll ahead of schedule and we have begun treating patients in the pembrolizumab combination portion of the trial,” said Michel Detheux, Ph.D., president and chief executive officer of iTeos. “As we look ahead to the end of the year and to 2025, we believe iTeos is well-positioned to enter its next phase of growth. We look forward to providing updates on our emerging pipeline and presenting initial data in head and neck cancer and longer-term follow-up data from GALAXIES Lung-201 next year.” Program Highlights Belrestotug (EOS-448/GSK4428859A): IgG1 anti-TIGIT monoclonal antibody in development for the first-line treatment of locally advanced or metastatic PDL1-selected non-small cell lung cancer (NSCLC) and for the first-line treatment of PD-L1 positive recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) in collaboration with GSK GALAXIES Lung-301: Enrollment ongoing globally in randomized, double-blind Phase 3 registrational study assessing belrestotug + dostarlimab versus placebo + pembrolizumab in patients with first-line advanced, unresectable, or metastatic PD-L1 high NSCLC. EMA granted clearance to advance belrestotug 400mg + dostarlimab as the recommended Phase 3 dose, allowing for the activation of clinical sites in the EU First patient first dose achieved in the EU. GALAXIES Lung-201: Further interim data from Phase 2 platform study assessing belrestotug + dostarlimab doublet in first-line advanced / metastatic PD-L1 high NSCLC anticipated in 2025. GALAXIES H&N-202: Interim data from randomized Phase 2 platform study assessing belrestotug + dostarlimab doublet and a triplet with GSK’s investigational anti-CD96 antibody, nelistotug, versus dostarlimab in first-line patients with PD-L1 positive recurrent / metastatic HNSCC anticipated in 2025. TIG-006 HNSCC: Topline data from the first portion of TIG-006 study in cohorts 2C & 2D assessing belrestotug + dostarlimab doublet in first-line PD-L1 positive advanced / metastatic HNSCC anticipated in 2025. Adenosine Pathway Inupadenant (EOS-850): insurmountable small molecule antagonist targeting adenosine A2A receptor in second-line NSCLC One poster presentation on preclinical data and two mini oral presentations featuring translational and clinical data from the dose escalation portion of the Phase 2 A2A-005 trial with inupadenant and platinum-doublet chemotherapy in post-IO metastatic non-squamous NSCLC to be presented at the European Society for Medical Oncology Immuno-oncology (ESMO IO) Congress 2024. EOS-984: potential first-in-class small molecule inhibiting ENT1, a dominant transporter of adenosine involved in T cell metabolism, expansion, effector function, and survival Completed enrollment of monotherapy dose escalation and initiated dosing of first cohort of EOS-984 + pembrolizumab combination portion in the Phase 1 APT-008 trial.Two poster presentations on preclinical and translational data highlighting the novel mechanism of action, monotherapy and combination activity combination activity with anti-PD-1 therapy, and the adenosine signature biomarker to be presented at the ESMO IO Congress 2024.Topline data from the Phase 1 APT-008 trial anticipated in 2025. Third Quarter 2024 Financial Results Cash and Investment Position: The Company’s cash, cash equivalents, and investments position was $648.9 million as of September 30, 2024, as compared to $644.9 million as of September 30, 2023. Pro forma cash, cash equivalents, and investments position were $683.9 million as of September 30, 2024, inclusive of a $35.0 million milestone receivable relating to the dosing of the first patient in the GALAXIES Lung-301 clinical trial. The Company expects its cash balance to provide runway through 2027, which includes the potential initiation of multiple Phase 3 registrational trials assessing the belrestotug + dostarlimab doublet. The Company expects its cash balance to provide runway through 2027, which includes the potential initiation of multiple Phase 3 registrational trials assessing the belrestotug + dostarlimab doublet. Research and Development (R&D) Expenses: R&D expenses were $36.7 million and $107.9 million for the quarter and nine months ended September 30, 2024, respectively, as compared to $30.6 million and $85.5 million for the same quarter and same nine months of 2023, respectively. The increase compared to the comparative period was primarily due to increases in activities related to the belrestotug, inupadenant, and EOS-984 programs, and included the addition of new R&D employees hired to help advance these programs. General and Administrative (G&A) Expenses: G&A expenses were $12.1 million and $37.3 million for the quarter and nine months ended September 30, 2024, respectively, as compared to $12.6 million and $38.0 million for the same quarter and same nine months of 2023, respectively. The decrease was primarily due to decreases in recruiting expenses, commercial-related expenses, and various other general and administrative expenses. These were partially offset by an increase in compensation expenses for G&A employees. Net Income/Loss: Net loss was $45.4 million, or net loss of $1.05 per basic and diluted share for the quarter ended September 30, 2024, as compared to a net loss of $32.2 million, or a net loss of $0.90 per basic and diluted share for the quarter ended September 30, 2023. Net loss was $90.7 million, or net loss of $2.29 per basic and diluted share for the nine months ended September 30, 2024, as compared to a net loss of $82.1 million, or a net loss of $2.30 per basic and diluted share for the nine months ended September 30, 2023. About iTeos Therapeutics, Inc.iTeos Therapeutics is a clinical-stage biopharmaceutical company pioneering the discovery and development of a new generation of immuno-oncology therapeutics for patients. iTeos Therapeutics leverages its deep understanding of tumor immunology and immunosuppressive pathways to design novel product candidates with the potential to restore the immune response against cancer. The Company’s innovative pipeline includes three clinical-stage programs targeting novel, validated immunosuppressive pathways designed with optimized pharmacologic properties for improved clinical outcomes, including the TIGIT/CD226 axis and the adenosine pathway. iTeos Therapeutics is headquartered in Watertown, MA with a research center in Gosselies, Belgium. About Belrestotug (EOS-448/ GSK4428859A) Belrestotug is an Fc active human immunoglobulin G1, or IgG1, monoclonal antibody (mAb) targeting T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT), an important inhibitory receptor which contributes to the suppression of adaptive and innate immune responses against cancer. As an optimized high-affinity, potent anti-TIGIT mAb, belrestotug is designed to enhance the antitumor response through a multifaceted immune modulatory mechanism by engaging with TIGIT and FcγR, a key regulator of immune responses which induces cytokine release and antibody dependent cellular cytotoxicity (ADCC). The therapeutic candidate is progressing in multiple indications in collaboration with GSK. About Inupadenant (EOS-850) Inupadenant is a next-generation small molecule antagonist targeting adenosine A2A receptor (A2AR), the primary receptor on immune cells whose activation by adenosine suppresses innate and adaptive immune cell responses leading to inhibition of antitumor responses. Optimized for potency, high selectivity of A2AR, and activity at high adenosine concentrations in solid tumors, inupadenant is uniquely designed with its insurmountable profile to inhibit the ATP-adenosine pathway and has the potential for enhanced antitumor activity as compared to other A2AR antagonists in clinical development. The therapeutic candidate is in Phase 2 development. About EOS-984EOS-984 is a potential first-in-class small molecule targeting equilibrative nucleoside transporter 1 (ENT1) designed to inhibit the immunosuppressive activity of adenosine and restore immune cell proliferation. The therapeutic candidate has the potential to fully reverse the profound immunosuppressive action of adenosine on T and B cells and is in Phase 1 development. Internet Posting of InformationiTeos routinely posts information that may be important to investors in the 'Investors' section of its website at www.iteostherapeutics.com. The Company encourages investors and potential investors to consult our website regularly for important information about iTeos. Forward-Looking StatementsThis press release contains forward-looking statements. Any statements that are not solely statements of historical fact are forward-looking statements. Words such as “believe,” “anticipate,” “plan,” “expect,” “will,” “may,” “intend,” “prepare,” “look,” “potential,” “possible” and similar expressions are intended to identify forward-looking statements. These forward-looking statements include statements relating to the potential benefits of belrestotug, inupadenant, and EOS-984; our plans and expected milestones, including having further interim data from GALAXIES Lung-201 in 2025; having interim data from GALAXIES H&N-202 in 2025; having topline data from the first portion of TIG-006 study in cohorts 2C & 2D assessing belrestotug + dostarlimab doublet in first-line PD-L1 positive advanced / metastatic HNSCC in 2025; presenting clinical data on inupadenant and preclinical data from EOS-984 at ESMO-IO in December 2024; having topline data from the Phase 1 trial of EOS-984 in 2025; iTeos being well positioned to enter its next phase of growth; intentions around trial enrollment and recruitment; and our expectation that our cash balance will provide runway through 2027 across a number of impactful portfolio milestones. These forward-looking statements involve risks and uncertainties, many of which are beyond iTeos’ control. Actual results could materially differ from those stated or implied by these forward-looking statements as a result of such risks and uncertainties. Known risk factors include the following: the expected benefits and opportunities related to the agreement between iTeos and GSK may not be realized or may take longer to realize due to a variety of reasons, including any inability of the parties to perform their commitments and obligations under the agreement, challenges and uncertainties inherent in product research and development and manufacturing limitations; success in preclinical testing and early clinical trials does not ensure that later clinical trials will be successful, and early results from a clinical trial do not necessarily predict final results; interim and early data may change as more patient data become available and are subject to audit and verification procedures; the data for our product candidates may not be sufficient for obtaining regulatory approval to move into later stage trials or to commercialize products; iTeos may encounter unanticipated costs or may expend cash more rapidly or more slowly than currently anticipated due to challenges and uncertainties inherent in product research and development and biologics manufacturing; iTeos may not be able to execute on its business plans, including meeting its expected or planned regulatory milestones and timelines, research and clinical development plans, and bringing its product candidates to market, for various reasons, some of which may be outside of iTeos’ control, including possible limitations of company financial and other resources, manufacturing limitations that may not be anticipated or resolved for in a timely manner, negative developments in the field of immuno-oncology, such as adverse events or disappointing results, including in connection with competitor therapies, and regulatory, court or agency decisions such as decisions by the United States Patent and Trademark Office with respect to patents that cover our product candidates; and those risks identified under the heading “Risk Factors” in iTeos’ Annual Report on Form 10-Q for the period ended September 30, 2024 filed with the Securities and Exchange Commission (SEC) as well as other SEC filings made by the Company which you are encouraged to review. Statements regarding the Company’s cash runway do not indicate when or if the Company may access the capital markets. Any of the foregoing risks could materially and adversely affect iTeos’ business, results of operations and the trading price of iTeos’ common stock. We caution investors not to place undue reliance on the forward-looking statements contained in this press release. iTeos does not undertake any obligation to publicly update its forward-looking statements other than as required by law. For further information, please contact: Investor Contact:Carl MauchiTeos Therapeutics, Inc.carl.mauch@iteostherapeutics.com Media Contact:media@iteostherapeutics.com

Phase 1Phase 2Phase 3ImmunotherapyFinancial Statement

06 Nov 2024

·pipelinereview.com

Arcus Biosciences Announces that Domvanalimab Plus Zimberelimab Improved Overall Survival in ARC-10, a Randomized Study in Patients with PD-L1-High Non-Small Cell Lung Cancer

HAYWARD, CA, USA I November 05, 2024 I Arcus Biosciences, Inc. (NYSE:RCUS), a clinical-stage, global biopharmaceutical company focused on developing differentiated molecules and combination therapies for patients with cancer, today announced results from Part 1 of ARC-10, a randomized, open-label, three-arm study evaluating domvanalimab, an Fc-silent anti-TIGIT monoclonal antibody, plus zimberelimab, an anti-PD-1 monoclonal antibody, (DZ) versus zimberelimab (Z) or chemotherapy in patients with front-line locally advanced or metastatic squamous or non-squamous non-small cell lung cancer (NSCLC) with PD-L1 tumor proportion score (TPS) ≥50% without the presence of any tumor genomic aberration or driver mutation for which a targeted therapy is approved. This study was conducted in partnership with Gilead Sciences. These results will be presented on November 8 in a late-breaking poster session at the Society for Immunotherapy of Cancer (SITC) 2024 Annual Meeting by Melissa L. Johnson, M.D., Director of the Lung Cancer Research Program, Sarah Cannon Research Institute, and investigator for the ARC-10 study. “Domvanalimab plus zimberelimab demonstrated a meaningful improvement in overall survival compared to zimberelimab alone, with a 36% reduction in risk of death and a median overall survival that will exceed two years,” said Melissa L. Johnson, M.D. “These data provide further evidence that co-inhibiting the TIGIT and PD-1 pathways may result in a greater therapeutic benefit over inhibition of the PD-1 pathway alone.” “These are the first results demonstrating an improvement in overall survival reported for domvanalimab and zimberelimab,” said Dimitry Nuyten, M.D., Ph.D., chief medical officer of Arcus. “They add to the growing body of evidence that domvanalimab, an Fc-silent anti-TIGIT antibody, may have a differentiated efficacy, safety and tolerability profile relative to published data from studies with Fc-enabled anti-TIGIT antibodies.” At the time of data cutoff (DCO, May 17, 2024), 98 patients were randomized and 95 received treatment in Part 1 of the study. The median follow-up was 24.5 months, and as of the DCO, 22 patients remained on treatment (DZ, n=11; Z, n=10; chemo, n=1). Patient baseline demographics were generally balanced across the arms, with a slight imbalance of more patients with adenocarcinoma, ECOG status 0, and brain metastasis favoring the chemotherapy arm. A summary of efficacy results is below. DZ and Z were generally well tolerated with no new safety concerns at the time of DCO. Treatment-related adverse events (TRAEs) leading to treatment discontinuation were higher for chemotherapy (23.5%) than for DZ (10.5%) and Z (7.5%). Infusion-related reactions were low (DZ, 7.9%; Z, 2.5%; chemotherapy, 0%). Grade ≥3 TRAEs were higher for chemotherapy (47.1%) than for DZ (21.1%) or Z (15.0%). TRAEs leading to death were lower for DZ (2.6%; n=1 sudden death) vs Z (10.0%; n=1 each sudden death, acute kidney injury, acute myocardial infarction, intestinal perforation) or chemotherapy (11.8%; n=1 each febrile neutropenia, ischemic stroke). Investors may dial into the earnings conference call at +1 (404) 975-4839 (local) or +1 (833) 470-1428 (toll-free), using Access Code: 940081, on Wednesday, Nov. 6, 2024, at 2:00 PM PT / 5:00 PM ET. Participants may also register for the call online using this link: https://www.netroadshow.com/events/login?show=4818aee3&confId=72838 . To access the live webcast and accompanying slide presentation, please visit the “Investors & Media” section of the Arcus Biosciences website at www.arcusbio.com . A replay will be available following the live event. About the ARC-10 Study ARC-10 was initially initiated and conducted as a randomized Phase 3 trial; the protocol was subsequently amended to evaluate domvanalimab plus zimberelimab versus pembrolizumab (part 2). Part 1 of the ARC-10 study is a multicenter, randomized, open-label study for patients with front-line locally advanced or metastatic squamous or non-squamous NSCLC with PD-L1 TPS ≥50% without the presence of any tumor genomic aberration or driver mutation for which a targeted therapy is approved. The study randomized patients 2:2:1 across the three study arms to receive every three weeks: (1) 15 mg/kg of domvanalimab plus 360 mg/kg of zimberelimab, (2) 360 mg/kg of zimberelimab or (3) platinum doublet chemotherapy in countries where anti-PD-(L)1 monotherapy was not yet standard of care. The primary endpoint was PFS per Response Evaluation Criteria in Solid Tumors (RECIST 1.1). The secondary endpoints were OS, confirmed ORR and safety. About Domvanalimab Domvanalimab is the most clinically advanced Fc-silent investigational monoclonal antibody that was specifically designed with Fc-silent properties to block and bind to the T-cell immunoreceptor with Ig and ITIM domains (TIGIT), a checkpoint receptor on immune cells that acts as a brake on the anticancer immune response. By binding to TIGIT with Fc-silent properties, domvanalimab is believed to work by freeing up immune-activating pathways and activating immune cells to attack and kill cancer cells without depleting the peripheral regulatory T cells important in avoiding immune-related toxicity. Combined inhibition of both TIGIT and programmed cell death protein-1 (PD-1) is believed to significantly enhance immune cell activation, as these checkpoint receptors play distinct, complementary roles in anti-tumor activity. Domvanalimab is being evaluated in combination with anti-PD-1 monoclonal antibodies, including zimberelimab, as well as other investigational cancer immunotherapies and A2a/A2b adenosine receptor antagonist etrumadenant, in multiple ongoing and planned early and late-stage clinical studies in various tumor types. About Zimberelimab Zimberelimab is an anti-programmed cell death protein-1 (PD-1) monoclonal antibody that binds PD-1, with the goal of restoring the anti-tumor activity of T cells. Zimberelimab has demonstrated high affinity, selectivity and potency in various tumor types. Zimberelimab is being evaluated in the U.S. and globally as a foundational anti-PD-1 treatment option in multiple ongoing and planned early and late-stage clinical studies in combination with other immunotherapies, including investigational Fc-silent anti-TIGIT monoclonal antibody domvanalimab and A2a/A2b adenosine receptor antagonist etrumadenant. Guangzhou Gloria Biosciences Co. Ltd., which holds commercialization rights for zimberelimab in greater China, has obtained approval for zimberelimab for the treatment of recurrent or metastatic cervical cancer and for relapsed or refractory classical Hodgkin’s lymphoma. Zimberelimab is not approved for any use in the U.S. or other regions outside of China. Gloria conducts its development and commercialization activities independent of Arcus and Gilead. Domvanalimab and zimberelimab are investigational molecules. Arcus and Gilead have not received approval from any regulatory authority for any commercial use globally, and their safety and efficacy for the treatment of lung cancer have not been established. About Arcus Biosciences Arcus Biosciences is a clinical-stage, global biopharmaceutical company developing differentiated molecules and combination medicines for people with cancer. In partnership with industry collaborators, patients and physicians around the world, Arcus is expediting the development of first- or best-in-class medicines against well-characterized biological targets and pathways and studying novel, biology-driven combinations that have the potential to help people with cancer live longer. Founded in 2015, the company has expedited the development of multiple investigational medicines into clinical studies, including new combination approaches that target TIGIT, PD-1, HIF-2a, CD73, dual A2a/A2b receptor, CD39, and AXL. For more information about Arcus Biosciences’ clinical and preclinical programs, please visit www.arcusbio.com . SOURCE: Arcus Biosciences

Clinical ResultImmunotherapyPhase 3Drug ApprovalASCO

100 Deals associated with Etigilimab

External Link

KEGG	Wiki	ATC	Drug Bank
D11593	-	-	-

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Fallopian Tube Clear Cell Adenocarcinoma	Phase 2	US	The University of Texas MD Anderson Cancer Center	30 Aug 2021
Recurrent Ovarian Clear Cell Adenocarcinoma	Phase 2	US	The University of Texas MD Anderson Cancer Center	30 Aug 2021
Recurrent Platinum-Resistant Fallopian Tube Carcinoma	Phase 2	US	The University of Texas MD Anderson Cancer Center	30 Aug 2021
Recurrent Platinum-Resistant Ovarian Carcinoma	Phase 2	US	The University of Texas MD Anderson Cancer Center	30 Aug 2021
Recurrent Platinum-Resistant Primary Peritoneal Carcinoma	Phase 2	US	The University of Texas MD Anderson Cancer Center	30 Aug 2021
Recurrent Primary Peritoneal Clear Cell Adenocarcinoma	Phase 2	US	The University of Texas MD Anderson Cancer Center	30 Aug 2021
Locally Advanced Malignant Solid Neoplasm	Phase 2	US	Mereo BioPharma Group Plc	23 Mar 2021
Locally Advanced Malignant Solid Neoplasm	Phase 2	GB	Mereo BioPharma Group Plc	23 Mar 2021
Metastatic Solid Tumor	Phase 2	US	Mereo BioPharma Group Plc	23 Mar 2021
Metastatic Solid Tumor	Phase 2	GB	Mereo BioPharma Group Plc	23 Mar 2021

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03119428 (Pubmed \| Clin Cancer Res) Manual	Phase 1	Solid tumor	33	Etigilimab alone (Phase 1a)	pybwfeqqxe(pktelfiaeb) = The most commonly reported adverse events (AE) were rash (43.5%), nausea (34.8%), and fatigue (30.4%) in Phase 1a and decreased appetite (50.0%), nausea (50.0%), and rash (40%) in Phase 1b. ippxvrpvqv (vxaienirlz ) View more	Positive	29 Nov 2021
NCT03119428 (Pubmed \| Clin Cancer Res) Manual	Phase 1	Solid tumor	33	EtigilimabNivolumab (Phase 1b)		Positive	29 Nov 2021
NCT03119428 (P289, SITC2018)	Phase 1	Advanced Malignant Solid Neoplasm TIGIT	18	Etigilimab (OMP-313M32)	imbewlwoyy(uwhqaqcdkf) = 5.5% sjpitnnxmh (nqgvtybhit ) View more	Positive	06 Nov 2018
NCT03119428 (Corporate Publications) Manual	Phase 1	Solid tumor	18	OMP-313M32	yamygwgwxk(vzjpzmvofe) = mkbwxszirj ydnunbgqox (numvvimdut ) View more	Positive	03 Oct 2018

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis