Gilead And Merus Announce Collaboration To Discover Novel Antibody-Based Trispecific T-Cell Engagers

On March 6, 2024 Gilead Sciences, Inc. (Nasdaq:GILD) and Merus N.V. (Nasdaq:MRUS) reported a research collaboration, option and license agreement to discover novel dual tumor-associated antigens (TAA) targeting trispecific antibodies (Press release, Gilead Sciences, MAR 6, 2024, View Source [SID1234640876]). Gilead and Merus agreed to collaborate on the use of Merus’ proprietary Triclonics platform along with Gilead’s oncology expertise to research and develop multiple, separate preclinical research programs.

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Merus is a clinical-stage oncology company developing innovative, full-length, multispecific antibodies (Biclonics and Triclonics), referred to together as Multiclonics, that are generated by a proprietary common light chain technology. The Triclonics or trispecific platform provides the unique opportunity to design antibodies capable of simultaneously binding to three targets at once.

"We have seen the successful application of bispecific antibodies as an immune-modulating modality used to treat cancer. We are now looking ahead to the development of additional multispecific antibodies capable of driving robust anti-tumor immune responses with an improved efficacy and safety profile," said Flavius Martin, M.D., Executive Vice President, Research, Gilead Sciences. "We are excited to explore the potential of Merus’ differentiated Triclonics platform to discover and advance transformative new cancer therapies as we deepen our portfolio across oncology indications."

"We are looking forward to working with Gilead to develop novel T-cell engager antibodies using our Triclonics technology," said Hui Liu, Ph.D., Executive Vice President, Chief Business Officer & Head of Merus US. "We are grateful for our collaborations which represent opportunities for Merus to leverage our research capabilities to pursue innovative biology and to address significant unmet medical needs. Importantly, this collaboration represents the first for our proprietary Triclonics platform."

Terms of the Agreement

Under the terms of the agreement, Merus will lead early-stage research activities for two programs, with an option to pursue a third. Gilead will have the right to license programs developed under the collaboration after the completion of select research activities. If Gilead exercises its option to license any such program from the collaboration, Gilead will be responsible for additional research, development and commercialization activities for such program. Merus will receive an upfront cash payment of $56 million for initial targets as well as an equity investment by Gilead of $25 million in Merus common shares. Across all potential programs, Merus is also eligible to receive up to $1.5 billion including additional near term and option payments, potential development and commercialization milestones, as well as tiered royalties ranging from the mid-single to low-double digits on product sales should Gilead successfully commercialize a therapy from the collaboration. For the third potential program, Merus may opt-in to share 50/50 split of net profits and net losses, in lieu of future milestone and royalty payments.

Gilead does not exclude acquired IPR&D expenses from its non-GAAP financial measures. This transaction with Merus is expected to reduce Gilead’s GAAP and non-GAAP 2024 EPS by approximately $0.03 – $0.05.

iTeos Reports Fourth Quarter and Full Year 2023 Financial Results and Provides Business Updates

On March 6, 2024 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, reported financial results for the fourth quarter and full year ended December 31, 2023 and provided a business update (Press release, iTeos Therapeutics, MAR 6, 2024, View Source [SID1234640875]).

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"As we anticipate four clinical readouts across the portfolio, 2024 is poised to be a transformative year for iTeos," said Michel Detheux, Ph.D., president and chief executive officer of iTeos. "With the recent developments in the TIGIT field, we believe belrestotug is in an advantageous position and are excited for its future prospects. We look forward to sharing updates from our Phase 2 trials focused on 1L NSCLC and 1L HNSCC in 2024. Additionally, our strong comprehension of the adenosine pathway has enabled us to develop two innovative and optimized assets – inupadenant, an A2AR antagonist in a class of its own, and EOS-984, a potential first-in-class inhibitor targeting the novel mechanism of ENT1. With our strategic cash position and robust pipeline, we are focused on the execution of these clinical trials to deliver on our highly anticipated milestones this year."

Corporate Developments

On March 6, 2024, iTeos announced the appointment of Jill DeSimone to the Company’s Board of Directors. With over 40 years of global business expertise in life sciences, Ms. DeSimone is recognized for her role as President of U.S. Oncology at Merck & Co., Inc., where she established the company’s oncology division, growing it from less than $500 million in annual revenue to $9 billion in eight years.
On December 7, 2023, iTeos announced the appointment of David K. Lee to the Company’s Board of Directors. A seasoned pharmaceutical veteran with a proven track record of building successful businesses focused on oncology and rare diseases, Mr. Lee currently serves as the Chief Executive Officer of Servier Pharmaceuticals (U.S.), where he established and grew Servier Pharmaceuticals to a fully innovative oncology company with four commercialized products and a robust pipeline.
Program Highlights

Belrestotug (EOS-448/GSK4428859A): IgG1 anti-TIGIT monoclonal antibody targeting first-line non-small cell lung cancer (NSCLC) and head and neck squamous cell carcinoma (HNSCC) in collaboration with GSK

Preparation underway for Phase 3 registrational studies that will evaluate the belrestotug + dostarlimab doublet
GALAXIES Lung-201: topline data from Phase 2 platform trial assessing belrestotug + dostarlimab doublet in first-line advanced/metastatic NSCLC anticipated in 2024
GALAXIES H&N-202: enrollment ongoing in Phase 2 platform study assessing belrestotug + dostarlimab doublet and a triplet with GSK’s investigational anti-CD96 antibody (GSK’608) in first-line patients with PD-L1 positive recurrent / metastatic HNSCC
TIG-006 HNSCC: topline data from Phase 2 expansion trial assessing belrestotug + dostarlimab doublet in first-line PD-L1 positive advanced or metastatic HNSCC anticipated in 2024
TIG-006 mNSCLC: enrollment ongoing in Phase 1b expansion trial assessing belrestotug, dostarlimab, and chemotherapy triplet in first-line advanced or metastatic NSCLC
Continued advancement of Phase 1b trials exploring two novel triplets in advanced solid tumors: belrestotug + dostarlimab and GSK’s investigational anti-CD96 antibody (GSK’608), and belrestotug + dostarlimab and GSK’s investigational anti-PVRIG antibody (GSK’562)
Adenosine Pathway

Inupadenant (EOS-850): insurmountable small molecule antagonist targeting adenosine A2A receptor in second-line NSCLC

A2A-005: Data from the dose escalation portion of the Phase 2 trial with inupadenant and platinum-doublet chemotherapy in post-IO metastatic non-squamous NSCLC anticipated in late 2024.
EOS-984: first-in-class small molecule inhibiting equilibrative nucleoside transporter 1 (ENT1), a dominant transporter of adenosine on lymphocytes involved in T cell metabolism, expansion, effector function, and survival

Completed enrollment of the third dose cohort and continued advancement in the dose escalation of the Phase 1 trial in advanced malignancies
Abstract acceptance by The American Association for Cancer Research (AACR) (Free AACR Whitepaper) for EOS-984, which highlights preclinical data on the novel mechanism of action, monotherapy activity, and combination activity with anti-PD-1 therapy
Oral presentation by Matthew Vander Heiden, M.D., Ph.D., from the Koch Institute for Integrative Cancer Research in collaboration with iTeos Therapeutics on the role of ENT1 on the metabolism and the immune system in cancer at The SITC (Free SITC Whitepaper) Spring Scientific, Metabolism at the Hub of Cancer and Immunity in Miami, FL
Session: Influence of Nutrient Environment on Immune Response
Date and Time: Sunday, March 10, 2024, 9:10 AM – 10:10AM

Topline data from the Phase 1 trial anticipated in the second half of 2024
Fourth Quarter and Full Year 2023 Financial Results

Cash and Investment Position: The Company’s cash, cash equivalents, and investments position was $632.7 million as of December 31, 2023, as compared to $731.4 million as of December 31, 2022. The Company continues to expect its cash balance to provide runway through 2026.

Research and Development (R&D) Expenses: R&D expenses were $27.9 million for the fourth quarter and $113.3 million for the year ended December 31, 2023, as compared to $25.4 million for the fourth quarter and $97.4 million for the year ended December 31, 2022. The increases in each comparative period were 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 $12.4 million for the fourth quarter and $50.4 million for the year ended December 31, 2023, as compared to $11.1 million for the fourth quarter and $43.9 million for the year ended December 31, 2022. The increases were primarily due to increases in headcount and related costs and an increase in stock-based compensation compared to the prior year. The increases were partially offset by a decrease in recruiting costs.

Net Income/Loss: Net loss attributable to common shareholders was $30.6 million, or net loss of $0.85 per basic and diluted share for the quarter ended December 31, 2023, as compared to a net income of $20.5 million, or a net income of $0.57 per basic share and $0.54 per diluted share for the quarter ended December 31, 2022. Net loss was $112.6 million, or net loss of $3.15 per basic and diluted share, for the year ended December 31, 2023, as compared to a net income of $96.7 million, or net income of $2.72 per basic share and $2.56 per diluted share, for the year ended December 31, 2022.

Medigene to Present Favorable Safety Profile of TCR-T Cells with Costimulatory Switch Protein at AACR 2024

On March 6, 2024 Medigene AG (Medigene or the "Company", FSE: MDG1, Prime Standard), an immuno-oncology platform company focusing on the discovery and development of T cell immunotherapies for solid tumors, reported that it will present a poster at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (AACR) (Free AACR Whitepaper) 2024 taking place from April 5-10, 2024 in San Diego, USA as well as an oral presentation at the ELRIG-Forum 2024 to be held in Darmstadt, Germany on March 7, 2024 (Press release, MediGene, MAR 6, 2024, View Source [SID1234640873]).

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Poster presentation:

AACR 2024
View Source
Location: San Diego Convention Center, San Diego
Date: April 5-10, 2024

Details on the poster presentation are as follows:
Abstract title: TCR-gated control of costimulatory switch protein (CSP) activation in rTCR-T cells expressing PD1-41BB
Maja Buerdek, Petra U. Prinz, Kathrin Mutze, Andrea Coluccio, Stefanie Tippmer, Miriam Bosch, Giulia Longinotti, Mario Catarinella, Kathrin Davari, Christiane Geiger, Barbara Loesch, Kristy Crame, Dolores J. Schendel.
Session details: PO.IM01.13 – Adoptive Cell Therapies 1: Tumor Antigen-Specific T-cells and TCR-T, Sunday, April 7, 1:30 PM – 5:00 PM local time

The work to be presented shows that recombinant T cell receptor engineered T cells (rTCR-T cells), when armored and enhanced by the PD1-41BB CSP, exhibit superior TCR-T cell functionality and safety as well as a favorable safety profile, revealing the strong potential for improving treatment of cancer patients suffering from advanced solid tumor malignancies.

The abstract for this research has been published online at View Source!/20272/presentation/6084 and the poster will be available online after the conference at View Source." target="_blank" title="View Source." rel="nofollow">View Source

The Company is planning a first-in-human trial for MDG1015, a TCR-T therapy incorporating the CSP in gastric cancer, ovarian cancer, myxoid/round cell liposarcoma and synovial sarcoma with IND/CTA filing targeted for 2H 2024. MDG1015 is a first-in-class, third generation TCR-T therapy targeting NY-ESO-1/ LAGE-1a, armored and enhanced by the PD1-41BB CSP.

Oral presentation:

ELRIG-Forum 2024
View Source
Location: Darmstadtium Convention Centre, Darmstadt
Date and time: March 7, 2024, 11:10 – 11:30am local time
Presenter: Dr. Barbara Lösch, Head, Technology & Innovation
Title: Evolution by Innovation: Connecting the Dots of TCR-T Therapies

Dr. Lösch will provide an overview on the Company’s proprietary End-to-End (E2E) Platform and highlight various tools within the E2E Platform that can enhance TCR-T cell functionality, safety and efficacy for generation of best-in-class, differentiated TCR-T therapies.

This presentation will available on Medigene’s website on March 7, 2024: View Source

BeiGene to Present Clinical and Preclinical Data from Broad Portfolio and Pipeline at AACR Annual Meeting 2024

On March 6, 2024 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global oncology company, reported the presentation of emerging oncology pipeline data at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting April 5-10 in San Diego (Press release, BeiGene, MAR 6, 2024, View Source [SID1234640871]). BeiGene has nine abstracts scheduled for poster presentations at AACR (Free AACR Whitepaper).

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"Our presentations at this year’s AACR (Free AACR Whitepaper) showcase our ongoing development of tislelizumab combinations in solid tumors as we assess the clinical potential of multiple novel immuno-oncology candidates and make data-driven decisions for further development," said Lai Wang, Ph.D., Global Head of Research & Development at BeiGene. "More broadly, they reflect our deep commitment to discovering innovative new medicines for cancer patients, including by pioneering novel mechanisms like targeted degradation."

BeiGene will present results from the AdvanTIG-204 Phase 2 study of tislelizumab (anti-PD1) plus ociperlimab (anti-TIGIT) in first-line limited-stage small cell lung cancer (SCLC) as well as results of a biomarker study of the same doublet in the setting of first-line non-small cell lung cancer (NSCLC). An ongoing, global Phase 3 trial of ociperlimab plus tislelizumab in stage IV, PD-L1 high NSCLC, AdvanTIG-302, will complete enrollment this month (NCT04746924). An additional clinical presentation includes the first data from a Phase 1a dose escalation study of BGB-10188, a phosphatidylinositol 3 kinase delta (PI3Kδ) inhibitor, plus tislelizumab in patients with solid tumors.

BeiGene will also be presenting preclinical characterizations of several novel molecules from its internal discovery engine, including a CEA x 4-1BB bispecific antibody and a chimeric degradation activation compound (CDAC) targeting BTK, BGB-16673. Clinical data from an ongoing Phase 1 study of BGB-16673 in relapsed/refractory B-cell malignancies were presented at ASH (Free ASH Whitepaper) 2023, demonstrating clinical responses and a tolerable safety profile in heavily pre-treated patients with B-cell malignancies, including those with BTK inhibitor-resistant disease (NCT05006716).​

An additional preclinical presentation highlights the therapeutic potential of the triple-combination of tislelizumab with anti-LAG-3 (LBL-007) and anti-TIM-3 (surzebiclimab); this combination is being evaluated in an ongoing Phase 2 study in head and neck squamous cell carcinoma (NCT05909904).

BeiGene Presentations During AACR (Free AACR Whitepaper) 2024

Abstract Title

Abstract #

Presentation

Time (PDT)

Lead Author

Preclinical

Characterization of the correlation between BTK

degradation and tumor growth inhibition of the

BTK target protein degraders using PK/PD

modeling

2110

Monday, April 8

9 a.m. – 12:30 p.m.

Section 30

Board #1

Y. Wu

BGB-B167, a first-in-class 4-1BB/CEACAM5

bispecific antibody, exhibits potent in vitro and in

vivo anti-tumor activity and superior safety profile

in preclinical models

2371

Monday, April 8

9 a.m. – 12:30 p.m.

Section 38

Board #17

Z. Li

Translational assessment of triple combination

with tislelizumab (anti-PD-1), LBL-007 (anti-LAG-

3) and surzebiclimab (anti-TIM-3) highlights its

strong anti-tumor activity and clinical potential in

solid tumors such as HNSCC

4041

Tuesday, April 9

9 a.m. – 12:30 p.m.

Section 3

Board #17

H. Zhu

Clinical

Exploration of potential biomarkers correlated

with efficacy of ociperlimab (anti-TIGIT) plus

tislelizumab (anti-PD1) in 1L PD-L1+ non-small

cell lung cancer (NSCLC)

CT053

Monday, April 8

9 a.m. – 12:30 p.m.

Section 48

Board #3

S. Kim

A first in human, phase 1a, dose escalation study

of BGB 10188, a phosphatidylinositol 3 kinase

delta (PI3Kδ) inhibitor, + tislelizumab (anti-PD-1)

in patients with solid tumors

CT189

Tuesday, April 9

9 a.m. – 12:30 p.m.

Section 48

Board #17

R. Cosman

AdvanTIG-204: A phase 2, multicenter,

randomized, 3-arm, open-label study investigating

the preliminary efficacy and safety of ociperlimab

(anti-TIGIT) + tislelizumab (anti-PD-1) +

concurrent chemoradiotherapy (cCRT) in patients

with untreated limited-stage small cell lung cancer

(SCLC)

CT255

Tuesday, April 9

1:30 p.m. – 5 p.m. Section 48

Board #14

Y. Gong

BGB-A317-LBL-007-202 (NCT06010303): A

phase 2, randomized, active-controlled, open-

label study to evaluate the efficacy and safety of

LBL 007 (anti-LAG-3) in combination with

tislelizumab (TIS; anti-PD-1) plus chemotherapy

(chemo) as first-line (1L) treatment in patients

with unresectable locally advanced/metastatic

esophageal squamous cell carcinoma (ESCC)

CT274

Tuesday, April 9

1:30 p.m. – 5 p.m. Section 50

Board #4

S. Park

Liberty-201 (NCT05609370): Maintenance

fluoropyrimidine and bevacizumab with or without

anti-lymphocyte activation gene-3 (LAG-3)

antibody LBL-007 plus anti-programmed cell

death protein-1 (PD-1) antibody tislelizumab (TIS)

for patients (pts) with metastatic or unresectable

microsatellite stable (MSS)/mismatch repair

proficient (pMMR)colorectal cancer (CRC)

CT276

Tuesday, April 9 1:30 p.m. – 5 p.m.

Section 50

Board #6

H.-J. Lenz

BGB-LC-201 (NCT05635708): A phase 2, open-

label, multi-arm study of tislelizumab (TIS; anti-

PD-1) in combination with investigational agents

+/- chemotherapy as first-line treatment for

patients with locally advanced, unresectable, or

metastatic non-small cell lung cancer (NSCLC)

CT277

Tuesday, April 9

1:30 p.m. – 5 p.m. Section 50

Board #7

G. Blumenschein

About Tislelizumab

Tislelizumab is a uniquely designed humanized immunoglobulin G4 (IgG4) anti-programmed cell death protein 1 (PD‑1) monoclonal antibody with high affinity and binding specificity against PD‑1. It is designed to minimize binding to Fc-gamma (Fcγ) receptors on macrophages, helping to aid the body’s immune cells to detect and fight tumors.

Vedanta Biosciences to Host Investor Meetings at the Leerink Partners 2024 Global Biopharma Conference

On March 6, 2024 Vedanta Biosciences, a clinical-stage company that is developing a potential new category of oral therapies based on defined bacterial consortia, reported that management will host investor meetings at the Leerink Partners 2024 Global Biopharma Conference being held in Miami, FL from Monday, March 11 through Wednesday, March 13, 2024 (Press release, Vedanta Biosciences, MAR 6, 2024, View Source [SID1234640869]).

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