On April 14, 2023 Immune-Onc Therapeutics, Inc. ("Immune-Onc"), a private, clinical-stage cancer immunotherapy company developing novel biotherapeutics targeting myeloid checkpoints, reported encouraging Phase 1 dose escalation data for IO-108, a novel myeloid checkpoint inhibitor targeting Leukocyte Immunoglobulin-Like Receptor B2 (LILRB2, also known as ILT4) (Press release, Immune-Onc Therapeutics, APR 14, 2023, View Source [SID1234630101]). The data will be presented in an oral session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Orlando, Florida, April 18. Preclinical data for IO-312, a novel bispecific antibody targeting LILRB4 (ILT3) and CD3 (LILRB4 x CD3) will also be presented on April 18 as a late-breaking poster at AACR (Free AACR Whitepaper) 2023.

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We have great news to share this year at #AACR23! Data from our Ph 1 study show encouraging clinical benefit for IO-108 as a monotherapy & when combined with pembrolizumab. Don’t miss the oral presentation on Tue., April 18 at 4:05-4:15 PM ET (CT040)

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"We are very encouraged to see promising signs of clinical activity across multiple solid tumor types and a favorable safety profile with our first-in-class myeloid checkpoint inhibitor, IO-108," said Charlene Liao, Ph.D., chief executive officer and board chair of Immune-Onc. "Our data demonstrates the utility of IO-108 as a new therapeutic modality to address key unmet needs for patients with solid tumors that do not respond to, develop resistance to, or relapse following, treatment with T cell checkpoint inhibitors."

The Phase 1 dose escalation study of IO-108 is intended to evaluate primary objectives of safety and tolerability, and secondary and exploratory objectives of pharmacokinetics, immunogenicity, pharmacodynamic (PD) biomarker effects, and antitumor activity of IO-108 as a monotherapy and in combination with pembrolizumab in patients with advanced solid tumors. The trial enrolled 25 advanced cancer patients with relapsed/refractory solid tumors. Patients received escalating doses of IO-108 (60 mg -1800 mg) intravenously once every three weeks (Q3W). Treatment with IO-108 was well-tolerated to the maximum administered dose (1800 mg Q3W); the maximum tolerated dose was not reached. Among 23 evaluable patients (11 monotherapy, 12 combination therapy plus 1 crossover), results showed 1 complete response and 4 stable disease patients in the monotherapy cohorts and 3 partial responses and 4 stable disease patients in the combination cohorts.

The 4 responding patients remain on study with an ongoing treatment duration of 8 to 12+ months as of abstract submission. Clinical benefit correlated with baseline characteristics and post-treatment changes in PD biomarkers including reprogramming of myeloid cells and activation of T cells.

"Treating patients who are refractory to treatment with T-cell immune checkpoint inhibitors remains an ongoing challenge across many tumor types," said IO-108 Phase 1 investigator, Matthew H. Taylor, M.D., Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, Oregon. "I am very encouraged by these results, particularly the complete response to IO-108 monotherapy treatment in the Merkel cell carcinoma patient who had progressed on prior anti-PD-1 treatments. These findings suggest that LILRB2 is a critically important immunotherapy target."

The initial data from dose escalation supports further development of IO-108. The preliminary recommended Phase 2 dose (RP2D) is 1200 mg Q3W which is projected to achieve full receptor occupancy in at least 90% of patients. The ongoing IO-108 Phase 1 study is actively enrolling several biomarker-driven dose expansion cohorts, using IO-108 at RP2D as a monotherapy and in combination with anti-PD-1 antibodies (pembrolizumab, cemiplimab or tislelizumab), both in the U.S. and China.

Immune-Onc oral and poster presentation details are as follows:

Abstract Number: 9498
Title: A first-in-human phase 1 trial of IO-108, an antagonist antibody targeting LILRB2 (ILT4), as monotherapy and in combination with pembrolizumab in adult patients with advanced relapsed or refractory solid tumors: Dose escalation study
Presenter: Matthew H. Taylor, M.D., Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, Oregon
Session Title: Novel Immunotherapy Combination Clinical Trials
Session Date and Time: Tuesday, April 18, 2:30 p.m. – 4:30 p.m. ET
Presentation Number: CT040

Abstract Number: LB217
Title: A novel bispecific LILRB4/CD3 antibody with potent killing of monocytic acute myeloid leukemia cells
Presenter: Charlene Liao, Ph.D., chief executive officer of Immune-Onc Therapeutics, Inc.
Session Title: Late-Breaking Research: Immunology 2
Session Date and Time: Tuesday, April 18, 9:00 a.m. – 12:30 p.m. ET
Location: Poster Section 36, Poster Board #10

Abstracts and full session details can be accessed through the AACR (Free AACR Whitepaper) Online Program Planner

ABOUT IO-108

IO-108 is a fully human IgG4 monoclonal antibody with high affinity and specificity towards LILRB2 (also known as ILT4). It blocks the interaction of LILRB2 with multiple ligands that are involved in cancer-associated immune suppression, including HLA-G, ANGPTLs, SEMA4A and CD1d. Preclinical data presented at the 2020 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) annual meeting and the 2022 American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting demonstrate that IO-108 functions as a myeloid checkpoint inhibitor and promotes innate and adaptive anti-cancer immunity.

The ongoing Phase 1 study of IO-108 in adult cancer patients has completed dose escalation in the U.S. (NCT05054348) and is actively enrolling several expansion cohorts, as a monotherapy and in combination with anti-PD-1 antibodies (pembrolizumab, cemiplimab or tislelizumab), both in the U.S. and China. To date, IO-108 has been well tolerated with demonstrated clinical activity in multiple tumor types, both as a monotherapy and in combination with pembrolizumab.

On April 14, 2023 AstraZeneca reported that it will present new data across its diverse, industry-leading Oncology pipeline and portfolio at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, 14 to 19 April 2023 (Press release, AstraZeneca, APR 14, 2023, View Source [SID1234630100]).

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Data from 70 presentations will be featured, including eight oral presentations, a plenary presentation of the AEGEAN Phase III trial of Imfinzi (durvalumab) based regimen in resectable non-small cell lung cancer (NSCLC), and the first disclosures of preclinical data for five novel molecules across the Company’s Antibody Drug Conjugate (ADC), Cell Therapy and Epigenetics scientific platforms.

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: "It’s exciting to see our strategy to attack cancer from multiple angles come to life at AACR (Free AACR Whitepaper) this year through data from our proprietary antibody drug conjugates, next generation cell therapies and epigenetics molecules. Furthermore, results from the AEGEAN trial show the potential of treating lung cancer patients early with Imfinzi before and after surgery which reinforces the importance of diagnosing lung cancer early."

Improving outcomes for patients with resectable lung cancer with Imfinzi
A late-breaking presentation of the AEGEAN Phase III trial results will highlight the potential of a novel Imfinzi-based treatment before and after surgery for patients with resectable early-stage (IIA-IIIB) NSCLC. AEGEAN has met its two primary endpoints, demonstrating improvements in event-free survival and pathologic complete response with Imfinzi in combination with neoadjuvant chemotherapy before surgery and as adjuvant monotherapy versus neoadjuvant chemotherapy alone followed by surgery.

Delivering the next wave of ADCs with proprietary platform
Two oral presentations will feature the first preclinical and translational results for AZD9592, a bispecific ADC designed to deliver targeted chemotherapy to cancer cells with a topoisomerase inhibitor 1 (TOP1i) warhead using the Company’s proprietary linker technology.

AZD9592 binds to two known oncogenic drivers: epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition factor (cMET). These two drivers are often co-expressed in solid tumours including in NSCLC and head and neck squamous cell carcinoma (HNSCC). This is the Company’s first bispecific ADC to enter the clinic and shows a promising efficacy and safety profile in preclinical models, with evidence for DNA damage dependent tumour cell death as the mechanism of action.

In addition, the first preclinical results will be presented for another ADC, AZD5335, a promising therapeutic candidate for the treatment of certain ovarian cancers. This ADC has a folate receptor alpha (FRα) targeting antibody linked to a proprietary TOP1i warhead. A robust anti-tumour response is reported in FRα-expressing preclinical models that are resistant to another FRα ADC with a microtubule inhibitor warhead. In addition, AZD5335 is active in models with either high or low levels of target expression as detected by computational pathology.

Preclinical data for AZD8205, an ADC targeting B7-H4, will also be presented both as monotherapy and in combination with the PARP-1 selective inhibitor, AZD5305. Robust anti-tumour activity is evident in preclinical models across multiple B7-H4 positive tumour types, including ovarian and cholangiocarcinoma tumours, with combination therapy resulting in higher anti-tumour activity than monotherapy.

Building the next generation of cell therapies in solid tumours
In cell therapy, the first clinical data will be presented for C-CAR031, a novel transforming growth factor-beta (TGFβ) armoured Glypican 3 (GPC3) targeting chimeric antigen receptor T cell (CAR-T) therapy that is being investigated for liver cancer. Early results show it is well tolerated with promising anti-tumour activity seen with objective responses in several patients to date.

The CAR-T is based on AZD5851, a novel cell therapy that was designed by AstraZeneca, and is being developed and manufactured by Cellular Biomedicine Group (CBMG). AstraZeneca’s TGFβ armouring is designed to resist the immuno-suppressive tumour microenvironment and enhance the potential effectiveness of CAR-Ts in solid tumours.

In addition, the first preclinical data will be shared on AZD0754, a novel TGFβ armoured CAR-T targeting STEAP2, a protein commonly overexpressed in prostate cancer. This is the first cell therapy to be designed, manufactured and developed by AstraZeneca. The presentation will show encouraging preclinical safety data and supports future clinical development of this potential first-in-class CAR-T therapy.

First disclosure and preclinical data for an epigenetics molecule targeting PRMT5
Epigenetic therapy is one of AstraZeneca’s six core scientific areas of focus. The modality is the latest addition to the Company’s diverse portfolio, which is designed to attack cancer from multiple angles and redefine outcomes for patients with high unmet needs.

At AACR (Free AACR Whitepaper), the first preclinical data will be presented for the novel lead epigenetics molecule, AZ-PRMT5i-1, a potent methylthioadenosine phosphorylase (MTAP)-selective PRMT5 inhibitor with anti-tumour activity in MTAP-deleted tumours. Loss of the MTAP gene occurs across approximately 15% of all cancers, which provides an opportunity to use a biomarker selection strategy and also spare healthy tissue. The preclinical results demonstrate MTAP selectivity and promising anti-tumour activity.

Harnessing transformational technologies
Transformational technologies, including circulating tumour DNA (ctDNA), computational pathology, and data science and artificial intelligence (AI), underpin the success of progressing AstraZeneca’s pipeline. Several presentations at AACR (Free AACR Whitepaper) showcase the Company’s efforts to harness the power of these technologies to better understand complex cancer biology, identify and select patients for treatment and increase the probability of success in the clinic.

Key AstraZeneca presentations during AACR (Free AACR Whitepaper) 2023

Lead author

Abstract title

Presentation details

IO

Heymach, JV

CT005 – AEGEAN: A phase 3 trial of neoadjuvant durvalumab + chemotherapy followed by adjuvant durvalumab in patients with resectable NSCLC

Abstract #CT005

Plenary

Harnessing the Immune System in the Clinic

16 April 2023

14:45 – 15:00 ET

Iyer S

Immunomodulatory effects of ceralasertib in combination with durvalumab in NSCLC patients with progression on anti-PD-(L)1 treatment (HUDSON, NCT03334617)

Abstract #CT039

Clinical Trials Minisymposium

Novel Immunotherapy Combination Clinical Trials

18 April 2023

15:50 – 16:00 ET

ADCs

Gymnopoulos, M

First disclosure of AZD5335, a TOP1i-ADC targeting low and high FRα-expressing ovarian cancer with superior preclinical activity vs FRα-MTI ADC

Abstract #LB025 / 17

Poster

Late-Breaking Research: Experimental and Molecular Therapeutics 1

16 April 2023

13:30 – 17:00 ET

Comer, F

AZD9592: an EGFR-cMET bispecific antibody-drug conjugate (ADC) targeting key oncogenic drivers in non-small-cell lung cancer (NSCLC) and beyond

Abstract #5736

Minisymposium

New Tricks for Known Targets: Novel Approaches to Inhibit Oncogenic Signaling

18 April 2023

15:22 – 15:37 ET

McGrath, L

Evaluation of the relationship between target expression and in vivo anti-tumour efficacy of AZD9592, an EGFR/c-MET targeted bispecific antibody drug conjugate

Abstract #5737

Minisymposium

New Tricks for Known Targets: Novel Approaches to Inhibit Oncogenic Signaling

18 April 2023

15:37 – 15:52 ET

Cazes, A

Preclinical evaluation of a novel B7-H4-targeted antibody-drug conjugate AZD8205 as a single agent and in combination with novel PARP inhibitor and checkpoint blockade

Abstract #2947 / 25

Poster

Therapeutic Antibodies 2

17 April 2023

13:30 – 17:00 ET

Meric-Bernstam, F

TROPION-PanTumor03: Phase 2, multicenter study of datopotamab deruxtecan (Dato-DXd) as monotherapy and in combination with anticancer agents in patients (pts) with advanced/metastatic solid tumours

Abstract #CT058 / 16

Poster

Phase II and Phase III Clinical Trials in Progress

17 April 2023

9:00 – 12:30 ET

Bhavsar, D

Combination of T-DXd with the irreversible pan-HER TKI afatinib drives combination benefit in HER2-low gastric and lung tumours

Abstract #3999 / 22

Poster

Oncogenes and Tumour Suppressor Genes as Targets for Therapy 3

18 April 2023

9:00 – 12:30 ET

Wray, R.

Improving Treatment Outcomes: A Digital Solution for Remote Patient Monitoring of Stomatitis for Patients receiving Dato-DXd

Abstract #LB143 / 7

Poster

Late-Breaking Research: Population Sciences

17 April 2023

13:30 – 17:00 ET

Cell Therapy

van Dyk, D

Antitumour activity of AZD0754, a dnTGFbR2 armored STEAP2 targeted CAR-T therapy, in preclinical models of prostate cancer

Abstract #LB085 / 1

Poster

Late-Breaking Research: Immunology 1

17 April 2023

9:00 – 12:30 ET

Zhang, Q

First report of preliminary safety, efficacy, and pharmacokinetics of C-CAR031 (GPC3-specific TGFBRIIDN CAR-T) in patients with advanced HCC

Abstract #CT097 / 5

Poster

First-in-Human Phase I Clinical Trials 1

17 April 2023

13:30 – 17:00 ET

Epigenetics

Smith, JM

Identification of a novel series of MTAP-selective PRMT5 inhibitors, and first disclosure of AZ-PRMT5i-1

Abstract #3088 / 1

Poster

Targeted Drug Design and Development for Cancer Therapy

17 April 2023

13:30 – 17:00 ET

Lynch, J

AZ-PRMT5i-1: A potent MTAP-selective PRMT5 inhibitor with pharmacodynamic and monotherapy anti-tumour activity in MTAP-deleted tumours

Abstract #6272 / 10

Poster

Epigenetics

19 April 2023

9:00 – 12:30 ET

TDR1

Zhi Peng

A Multicenter Phase II Study of Savolitinib in Patients with MET-Amplified Gastroesophageal Junction Adenocarcinomas or Gastric Cancer

Abstract # CT152

Phase II Clinical Trials 1

17 April 2023

13:30 – 17:00 ET

ctDNA

Labrousse, P

The evolution of MRD assays; moving beyond the tumour-informed bespoke NGS panel

Abstract #LB293 / 6

Poster

Late-Breaking Research: Clinical Research 3

19 April 2023

9:00 – 12:30 ET

Russell, H

Evaluation of a tumour informed MRD assay with contrived breast cancer samples

Abstract #3384 / 27

Poster

Liquid Biopsies: Circulating Nucleic Acids and Circulating Tumour Cells 3

17 April 2023

13:30 – 17:00 ET

Munugalavadla V

Utility of ctDNA-based targeted methylation MRD assay for hematological malignancies

Abstract #3369 / 12

Poster

Liquid Biopsies: Circulating Nucleic Acids and Circulating Tumour Cells 3

17 April 2023

13:30 – 17:00 ET

Hartmaier, R

Baseline and on-treatment plasma-based genomics as a predictor of outcomes in SAVANNAH: savolitinib + osimertinib in EGFRm MET overexpressed/amplified NSCLC post-osimertinib

Abstract #LB294 / 7

Poster

Late-Breaking Research: Clinical Research 3

19 April 2023

9:00 – 12:30 ET

Data Science & AI

Arango G

Translating state-of-the-art deep learning predictions of IO treatment efficacy to clinical practice

Abstract #5359 / 8

Poster

Artificial Intelligence and Machine/Deep Learning 1

18 April 2023

13:30 – 17:00 ET

Arango G

Enhancing the utilization of deep learning to predict patient response in small immunotherapy cohorts using real world data

Abstract #1174

Minisymposium

Advancing Cancer Research Through an International Cancer Registry: AACR (Free AACR Whitepaper) Project GENIE Use Cases

16 April 2023

15:36 – 15:51 ET

Nikolau N

Improving survival prediction using flexible late fusion machine learning framework for multi-omics data integration

Abstract #5395 / 11

Poster

Artificial Intelligence and Machine/Deep Learning 2

18 April 2023

13:30 – 17:00 ET

Arango G

Improved identification of CHIP mutations from cell free DNA without matched normal samples using machine learning

Abstract #5360 / 9

Poster

Artificial Intelligence and Machine/Deep Learning 1

18 April 2023

13:30 – 17:00 ET

Ellen JG

Autoencoder-based multimodal prediction of survival for non-small cell lung cancer

Abstract #5373 / 22

Poster

Artificial Intelligence and Machine/Deep Learning 1

18 April 2023

13:30 – 17:00 ET

Computational Pathology

Potdevin, G

A first assessment of CD8-PET/CT with 89-Zr-Crefmirlimab as predictive biomarker for response to standard of care immunotherapy in patients with solid tumours

Abstract #3577 / 2

Poster

PET, MRI, and CT Imaging

18 April 2023

9:00 – 12:30 ET

Brieu, N

A unified computational pathology method to quantify HER2 expression from raw IHC and IF images in breast cancer

Abstract #5388 / 4

Poster

Artificial Intelligence and Machine/Deep Learning 2

18 April 2023

13:30 – 17:00 ET

On April 14, 2023 Merus N.V. (Nasdaq: MRUS) (Merus, the Company, we, or our), a clinical-stage oncology company developing innovative, full-length multispecific antibodies (Biclonics and Triclonics), reported the publication of an abstract for a poster presentation of early clinical data on the bispecific antibody petosemtamab in advanced gastric/esophageal adenocarcinoma (GEA) at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023 taking place in Orlando, Florida April 14-19, 2023 (Press release, Merus, APR 14, 2023, View Source [SID1234630099]).

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Petosemtamab, or MCLA-158, is a human IgG1 Biclonics designed to bind to cancer cells expressing epidermal growth factor receptor (EGFR) and leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5).

Petosemtamab is in clinical development in the expansion part of a phase 1/2 open-label, multicenter trial in advanced solid tumors, including advanced GEA.

Although petosemtamab has demonstrated promising clinical activity among pretreated gastric/esophageal adenocarcinoma (GEA) patients having EGFR gene amplification and/or overexpression, the Company has decided to pause further clinical exploration of the GEA cancer cohort at this time. The Company plans to prioritize investigating petosemtamab in head and neck squamous cell carcinoma, in view of the strong clinical activity observed in this cohort.

Information and observations from the cohort of GEA patients treated in the phase 1/2 trial include:

As of an October 24, 2022 data cutoff date, 14 previously treated GEA patients (pts) were treated with petosemtamab 1500 mg (IV) every two weeks
Patient Population:
Median age was 63 (range of 40-80); 79% were male
Median prior lines of systemic therapy was 3 (range 1-4); including platinum-based chemotherapy (36% of pts) and checkpoint inhibitors (14%)
14 pts were evaluable for efficacy, receiving ≥2 treatment cycles (≥8 weeks) with ≥1 post-baseline tumor assessment or experiencing early progressive disease
Antitumor activity among the 14 pts:
1 pt with tumor EGFR protein overexpression and gene copy number amplification (CNA) showed a confirmed sustained partial response (67% tumor reduction; response ongoing after 24 cycles);
3 pts had stable disease (1 with EGFR overexpression and gene CNA; 2 not evaluable for IHC), with tumor reductions of 2%, 17%, and 40%.
Petosemtamab continues to demonstrate a manageable safety profile:
Of 78 pts treated at the recommended phase 2 dose of 1500 mg every two weeks (escalation and all expansion cohorts), the most frequent AEs regardless of causality (all grades/G3-4) were rash (33%/0%), hypotension (26%/6%), dyspnea (26%/4%), nausea (26%/1%), dermatitis acneiform (24%/1%), blood magnesium decreased (19%/5%), erythema (19%/0%), diarrhea (19%/0%); IRRs (composite term) were reported in 74%/21% of pts, mostly at the first infusion, and all resolved. 5 pts (6%) discontinued treatment due to IRRs on Day 1.
Presentation Details:
Title: MCLA-158 (petosemtamab), an IgG1 bispecific antibody targeting EGFR and LGR5, in advanced gastric/esophageal adenocarcinoma (GEA)
Session: Phase II Clinical Trials 1
Date: Monday, April 17, 2023
Time: 1:30 – 5:30 p.m. ET
Poster #: 18
Abstract #: CT156

The abstract can be found on the conference website.

About Petosemtamab 
Petosemtamab, or MCLA-158, is a bispecific Biclonics low-fucose human full-length IgG1 antibody targeting the epidermal growth factor receptor (EGFR) and the leucine-rich repeat containing G-protein-coupled receptor 5 (LGR5). Petosemtamab is designed to exhibit three independent mechanisms of action including inhibition of EGFR-dependent signaling, LGR5 binding leading to EGFR internalization and degradation in cancer cells, and enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) activity.

On April 14, 2023 Merus N.V. (Nasdaq: MRUS) (Merus, the Company, we, or our), a clinical-stage oncology company developing innovative, full-length multispecific antibodies (Biclonics and Triclonics), reported the publication of an abstract for a plenary session oral presentation of interim clinical data on the bispecific antibody petosemtamab in previously treated head and neck squamous cell carcinoma (HNSCC) at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023 taking place in Orlando, Florida April 14-19, 2023 (Press release, Merus, APR 14, 2023, View Source [SID1234630098]).

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Petosemtamab, or MCLA-158, is a human IgG1 Biclonics designed to bind to cancer cells expressing epidermal growth factor receptor (EGFR) and leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5).

"We are excited by these data demonstrating clinically meaningful efficacy and durability of petosemtamab in previously treated head and neck cancer. We are looking forward to sharing additional details at the AACR (Free AACR Whitepaper) clinical trials plenary session and on our upcoming investor call," said Dr. Andrew Joe, Chief Medical Officer at Merus.

Petosemtamab (MCLA-158: EGFR x LGR5 Biclonics): Solid Tumors
Enrollment continues in dose expansion in the phase 1/2 trial, including in combination with Keytruda (pembrolizumab)

Petosemtamab is in clinical development in the expansion part of a phase 1/2 open-label, multicenter trial in advanced solid tumors, including previously treated head and neck squamous cell carcinoma (HNSCC). The Company also initiated a cohort investigating petosemtamab in combination with Keytruda in patients with untreated HNSCC, designed to evaluate safety and clinical activity in this population.

Plenary Session Oral Presentation: Clinical activity of MCLA-158 (petosemtamab), an IgG1 bispecific antibody targeting EGFR and LGR5, in advanced head and neck squamous cell cancer (HNSCC)

The oral presentation will include updated interim data from the ongoing phase 1/2 clinical trial and will be presented by the Principal Investigator, Dr. Ezra EW Cohen, Moores Cancer Center, UC San Diego Health.

The abstract provides information and observations from the ongoing phase 1/2 trial, including:

As of a November 28, 2022 data cutoff date, 49 previously treated HNSCC patients (pts) were treated with petosemtamab 1500 mg IV every two weeks
Patient Population:
Median age was 63 (range of 31-77); 78% were male
Median prior lines of systemic therapy was 2 (range 1-4); including anti-PD-1/PD-L1 in 96% of pts, platinum-based chemotherapy in 92% of pts; 2 pts received prior cetuximab
Most frequent primary tumor locations were oropharynx (35%), oral cavity (31%), and larynx (16%)
42 pts were evaluable for efficacy, receiving ≥2 treatment cycles (≥8 weeks) with ≥1 post-baseline tumor assessment or experiencing early progressive disease:
Antitumor activity among the 42 pts:
Overall responses rate (ORR) was 35.7% (15/42), by RECIST 1.1 per investigator assessment including 1 complete response (ongoing after 18 months), 12 partial responses (PRs), and 2 unconfirmed PRs with treatment ongoing at the data cutoff
Median duration of response (DOR) was 6.0 months (95%CI=3.3-not calculable) and median progression-free survival was 5.0 months (95%CI=3.2-6.8) with 17 pts continuing on therapy at the data cutoff
Petosemtamab continued to demonstrate a manageable safety profile:
Of 78 pts treated at the recommended phase 2 dose of 1500 mg every two weeks (escalation and all expansion cohorts), the most frequent AEs regardless of causality (all grades/G3-4) were rash (33%/0%), hypotension (26%/6%), dyspnea (26%/4%), nausea (26%/1%), dermatitis acneiform (24%/1%), blood magnesium decreased (19%/5%), erythema (19%/0%), diarrhea (19%/0%); IRRs (composite term) were reported in 74%/21% of pts, mostly at the first infusion, and all resolved. 5 pts (6%) discontinued treatment due to IRRs on Day 1.
Presentation Details:
Title: Clinical activity of MCLA-158 (petosemtamab), an IgG1 bispecific antibody targeting EGFR and LGR5, in advanced head and neck squamous cell cancer (HNSCC)
Session Category: Clinical Trials Plenary Session
Session: Promising Novel Antitumor Strategies in Early Phase Clinical Trials
Date: Monday, April 17, 2023
Time: 10:15 a.m. – 12:15 p.m. ET
Presentation #: CT012

Regulatory Update

Merus met with the U.S. Food and Drug Administration (FDA) in an end-of-phase meeting to discuss interim results from the previously treated HNSCC cohort of the petosemtamab phase 1/2 trial. The FDA recognized recurrent or metastatic HNSCC represents an area of unmet medical need, and provided clear recommendations for the path to potential registration.

Based on the strong clinical data and discussions with the FDA, Merus believes a randomized clinical trial in previously treated (2L/3L) or untreated (front-line) HNSCC may support a possible registration. Additionally, Merus believes a randomized registration trial in HNSCC with an overall response rate endpoint could potentially support accelerated approval and the overall survival results from the same study could potentially verify its clinical benefit to support regular approval. The Company plans to continue to acquire data to confirm a suitable dose for future randomized clinical trials.

"Based on our end-of-phase meeting with the FDA, we believe we have optionality in our development path for petosemtamab in head and neck squamous cell carcinoma and are excited to continue investigation of this important new potential therapy for patients," said Bill Lundberg, M.D., President, Chief Executive Officer at Merus. "I’m proud of the progress we are making towards our ambition to become a fully integrated US product company."

The abstract can be found on the conference website.

Company Conference Call and Webcast Information
Merus will hold a conference call and webcast for investors on April 17, 2023 at 6:30 p.m. ET. A replay will be available after the completion of the call in the Investors and Media section of our website for a limited time.

Date & Time: April 17, 2023 at 6:30 p.m. ET
Webcast link: Available on our website
Dial-in: Toll Free: 1 (800) 715-9871 / International: 1 (646) 307-19631
Conference ID: 4032258

About Petosemtamab
Petosemtamab, or MCLA-158, is a bispecific Biclonics low-fucose human full-length IgG1 antibody targeting the epidermal growth factor receptor (EGFR) and the leucine-rich repeat containing G-protein-coupled receptor 5 (LGR5). Petosemtamab is designed to exhibit three independent mechanisms of action including inhibition of EGFR-dependent signaling, LGR5 binding leading to EGFR internalization and degradation in cancer cells, and enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) activity.

On April 14, 2023 TransCode Therapeutics, Inc. (NASDAQ: RNAZ) ("TransCode" or the "Company"), the RNA Oncology Company committed to more effectively treating cancer using RNA therapeutics, reported that it has entered into a Common Stock Purchase Agreement (the "Agreement") with White Lion Capital, LLC ("White Lion Capital") an investor in the glioblastomas / oncology sector (Press release, TransCode Therapeutics, APR 14, 2023, View Source [SID1234630095]). The Agreement provides the Company with the right to sell White Lion Capital up to approximately $1.08 million of its common stock until May 31, 2023, subject to certain limitations and conditions. The Company intends to use the net proceeds from the transaction for working capital and general corporate purposes.

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The shares of common stock described above will be offered by the Company pursuant to a "shelf" registration statement on Form S-3 (File No. 333-268764) previously filed with the Securities and Exchange Commission (the "SEC") on December 13, 2022, and declared effective by the SEC on December 16, 2022. The offering of the shares of common stock will be made only by means of a prospectus, including a prospectus supplement, forming a part of the effective registration statement. Electronic copies of the final prospectus supplement and accompanying prospectus were filed with the SEC and may be obtained on the SEC’s website at View Source

This press release shall not constitute an offer to sell or a solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction.