On April 12, 2022 Trishula Therapeutics, Inc., a clinical stage, privately held company developing TTX-030, a first-in-class investigational anti-CD39 antibody in advanced cancers, reported preliminary results from an ongoing Phase 1 trial evaluating TTX-030 in combination with budigalimab (investigational anti-PD-1) and FOLFOX for the first-line treatment of patients with locally advanced/metastatic HER2 negative gastric or gastroesophageal junction cancer (Press release, Trishula Therapeutics, APR 12, 2022, View Source [SID1234612101]). Study results were presented in an oral presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in New Orleans. The data presented demonstrates that TTX-030 combination treatment was generally well-tolerated and showed encouraging signs of anti-tumor activity.

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"The response rates including in patients with PD-L1 low tumors seen in this preliminary analysis are very encouraging and support the potential of TTX-030 to impact the standard of care for patients with gastric and gastroesophageal cancer," said Zev Wainberg, M.D., Professor of Medicine at UCLA and co-director of the UCLA GI Oncology Program. "We look forward to the complete findings from this trial and the further advancement of this promising treatment approach."

Preliminary efficacy and safety results were presented as of an interim data cut of March 1, 2022. A total of 44 patients were enrolled. Twenty-six (26) patients were still on study treatment, and the median duration on study was 214 days (range 8-464+ days). Among 40 efficacy-evaluable patients, 21 patients (25 patients including unconfirmed) achieved best overall response of partial response or better including 4 CRs: ORR=52.5% (62,5% including unconfirmed), and disease-control rate = 92.5%. Thirty-seven (37) of the efficacy-evaluable patients had known PD-L1 Combined Positive Score (CPS); response rates in patients with CPS ≥1 were 65% (77% including unconfirmed).

Twenty-seven of 44 patients (61%) experienced at least one adverse event (AE) of any grade considered related to TTX-030 (investigator assessment), including 9 patients (20.5%) with Grade 3/4 AEs. Adverse events were overall consistent with those seen with standard-of-care (chemotherapy plus anti-PD-1).

"Our data highlighted at AACR (Free AACR Whitepaper) represents the first promising clinical findings of an anti–CD39 antibody in patients with gastric cancers and supports the role of TTX-030 in reversing adenosine-mediated immunosuppression," said Anil Singhal, Chief Executive Officer. "We look forward to the continued advancement of this clinical study of TTX-030, which we believe has the potential to significantly improve the treatment paradigm for cancer patients."

AACR Oral Presentation Details:

Title: Safety and efficacy of TTX-030, an anti-CD39 antibody, in combination with chemoimmunotherapy for the 1st line treatment of locally advanced or metastatic gastric/GEJ cancer.

Abstract Number: 8213

About TTX-030 Phase 1 Trial

The ongoing Phase 1 trial is evaluating TTX-030 in different treatment combinations in patients with advanced unresectable or metastatic cancer of the stomach or gastroesophageal junction with HER2-negative disease and no prior treatment for metastatic disease or adjuvant therapy within six months of enrollment. The primary endpoint is safety and tolerability with secondary endpoints of overall response (ORR) assessed using Response Evaluation criteria in Solid Tumors (RECIST/iRECIST) and progression free survival. Patients receive treatment with mFOLOFOX, Budigaglimab and TTX-330 030 on a 28-day cycle until disease progression.

On April 12, 2022 The Precision Cancer Consortium (PCC) reported its formation as a new collaboration of pharmaceutical companies with a shared vision of enabling access to comprehensive testing for all cancer patients globally (Press release, The Precision Cancer Consortium, APR 12, 2022, View Source [SID1234612100]). The PCC will drive a variety of initiatives aimed at increasing patient access to precision diagnostics using comprehensive genomic testing, including next generation sequencing (NGS). The PCC’s founding members are Bayer, GlaxoSmithKline, Novartis, and Roche.

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Despite significant treatment advances that target specific molecular alterations in cancer cells, many patients still do not undergo biomarker testing necessary to inform their treatment options. Currently, stakeholders may not be aware of the benefits of comprehensive genomic testing or may not know how to translate results into appropriate patient care. In addition to limited use of precision diagnostics in routine cancer treatment, there are other challenges related to recruiting patients into research studies investigating targeted therapies in biomarker subgroups defined by genomic alterations.

"With cancer, the earlier patients are diagnosed and begin treatment, the better their outcomes tend to be. Precision diagnostics, including comprehensive genomic testing, are an important part of developing treatment plans that can help patients," explains Espen Walker (Roche), Chair of the Precision Cancer Consortium. "The PCC is focused on addressing these barriers across the cancer ecosystem with the aim of improving outcomes for patients."

PCC’s objective is to support efforts to improve patient access to comprehensive genomic testing in routine care and in clinical trials. The PCC currently has two workstreams. The first workstream aims to remove barriers to access and increase educational awareness on the value of genomic testing for healthcare stakeholders – including patients, healthcare providers, and health care systems. The second workstream focuses on improving efficiencies in genomic biomarker testing in clinical trials. The PCC will not endorse or promote any diagnostic or therapeutic products or services.

The PCC is open and welcomes additional members. The PCC invites pharmaceutical or biotechnology organizations engaging in or supporting the discovery, development, research of interventions and diagnostics related to precision oncology to join this important initiative. Membership inquiries can be directed to the PCC using the contact information below.

On April 12, 2022 Bridge Biotherapeutics (KQ288330), a South Korean clinical-stage biotechnology company focused on developing novel drugs for cancer, fibrosis and inflammation, reported that the preclinical data poster of BBT-207 was unveiled at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2022 being held from April 8-13 (Press release, Bridge Biotherapeutics, APR 12, 2022, View Source [SID1234612098]).

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BBT-207, a novel fourth-generation Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI) currently under IND-enabling preclinical development, is the company’s first internally discovered drug candidate with potent activity and efficacy against a broad range of EGFR mutations in non-small cell lung cancer (NSCLC), including C797S double mutations which arise after third-generation EGFR TKI treatment.

During the poster presentation, the company highlighted the potent anti-tumor efficacy of BBT-207, observed through both in-vitro and in-vivo studies. Biochemical and cellular in-vitro efficacy data showed that BBT-207 is highly potent against EGFR C797S double mutations inclusive of Del19/C797S (DC) and L858R/C797S (LC) as well as driver mutations including Del19 and L858R. The results obtained from the in-vitro biochemical study demonstrated that the IC50 for EGFR tyrosine kinase inhibition activity was achieved at 0.8 nM against DC and LC double mutations, while Osimertinib showed 304.4 nM and 573.7 nM. Further, an in-vitro study utilizing Ba/F3 cell lines showed that BBT-207 is mutant selective and has minimal effect on wild-type EGFR.

The poster also highlighted the pharmacokinetics (PK) data of BBT-207 in animal models, which showed that the plasma concentrations of the drug candidate remained above the IC50 (0.7-11.8 ng/mL) and IC90 values (5.2-39.9 ng/mL, unpublished) for triple, double, and single mutations in Ba/F3 cell lines.

In addition, in-vivo efficacy studies have shown that BBT-207 boasts robust efficacy and induced tumor regressions over 14 days in both single (driver) mutations and C797S double mutations, when dosed at 40mg/kg QD. Further, BBT-207 demonstrated dose dependent tumor regression efficacy against T790M double mutations, which indicates the potential of BBT-207 as a broad-spectrum frontline treatment for NSCLC.

"We are highly encouraged that our data presented at the AACR (Free AACR Whitepaper) annual meeting strongly supports that BBT-207 has the potential to be positioned as the best-in-class fourth-generation EGFR TKI targeting C797S double mutations as well as an advanced frontline treatment for EGFR-driven NSCLC," and "while third-generation EGFR TKIs are emerging as early-stage treatments, unmet medical needs relating to C797S mutations still exist. We look forward to entering the Phase 1 clinical study in metastatic NSCLC patients who harbor C797S mutations, in order to bring a novel therapy in the advanced cancer disease area," stated Jimmy Jin M.D., Ph.D., the Head of Discovery Biology of Bridge Biotherapeutics.

Bridge Biotherapeutics is also developing BBT-176, a fourth-generation EGFR TKI candidate that is designed to inhibit C797S triple mutations. As third-generation EGFR TKIs, such as Osimertinib, have emerged as first-line treatments for EGFR-mutant NSCLC, Bridge Biotherapeutics has reinforced its oncology pipelines by nominating BBT-207 in November 2021, as the first internally-discovered EGFR TKI inhibiting C797S double mutations. Armed with BBT-176 and BBT-207, the company aims to offer NSCLC patients comprehensive treatment solutions.

A copy of the poster presented at the AACR (Free AACR Whitepaper) 2022 annual meeting is available at: https://bit.ly/3O4xOJp

The details of the presentation are as follows:

Presentation Title: BBT-207, a 4th Generation EGFR TKI With Broad-Spectrum Activity to Both Treatment-Emergent and Drug- naïve Mutants for the Treatment of NSCLC

Session Category: Experimental and Molecular Therapeutics

Session Title: Tyrosine Kinase and Phosphatase Inhibitors (PO.ET06.01)

Session Date & Time: Tuesday, April 12, 2022, 1:30 pm — 5:00 pm

Abstract Number: 3346

On April 12, 2022 Enzychem Lifesciences (KOSDAQ: 183490), a late-stage biopharmaceutical company, reported that the abstract has been accepted for an Oral Proffered Paper at the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO) 2022 annual meeting, which will be held in hybrid on June 23-25, 2022 in Toronto, Canada (Press release, Enzychem Lifesciences, APR 12, 2022, View Source [SID1234612096]).

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The abstract highlights the new clinical data from Enzychem’s Phase 2 US clinical trial evaluating EC-18 in head and neck cancer (HNC) patients with chemoradiation-induced oral mucositis (CRIOM). It will be presented by the highest enrolling site’s principal investigator, Christina Henson, M.D, a board-certified Radiation Oncologist and Residency Program Director for Radiation Oncology at the University of Oklahoma.

"I am honored to present Enzychem’s clinical data at the MASCC/ISOO 2022 annual meeting," said Dr. Christina Henson. "This compelling Phase 2 data shows that EC-18 will become an important treatment option for cancer patients undergoing chemoradiation therapy with currently no approved therapies."

The details of the presentation are as follows:

Title: Phase 2, Randomized, Double-Blind Trial of EC-18 to Alter the Severity and Course of Oral Mucositis Due to Chemoradiation for Head and Neck Cancer
Presenter: Christina Henson, M.D
Date: June 24th, 2022

On April 12, 2022 Immune-Onc Therapeutics, Inc. ("Immune-Onc"), a private, clinical-stage cancer immunotherapy company developing novel biotherapeutics targeting myeloid checkpoints, reported that the first patient has been dosed in the Company’s Phase 1 clinical trial of IO-202, a first-in-class myeloid checkpoint inhibitor targeting Leukocyte Immunoglobulin-Like Receptor B4 (LILRB4, also known as ILT3) for the treatment of patients with advanced solid tumors (NCT05309187) (Press release, Immune-Onc Therapeutics, APR 12, 2022, View Source [SID1234612095]).

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"We are very pleased to announce the initiation of our Phase 1 study of IO-202 in solid tumors, a significant achievement in our development strategy targeting the LILRB family of myeloid checkpoints to overcome immune suppression in the tumor microenvironment," said Paul Woodard, M.D., chief medical officer of Immune-Onc. "We believe by targeting the LILRB4 checkpoint, IO-202 may reverse the immunosuppressive effects of tumor associated monocytic myeloid cells, enhance dendritic cell function, and promote T cell activation – thereby, unleashing the antitumor activities of the immune system and increasing the therapeutic benefit of T cell checkpoint inhibitors. We look forward to conducting this study and assessing the potential of IO-202 as a monotherapy and in combination with pembrolizumab across multiple solid tumor types."

This study consists of two parts: a dose escalation portion to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of IO-202 alone and in combination with pembrolizumab, an anti-PD-1; and a dose expansion portion using the recommended Phase 2 dose of IO-202 in combination with pembrolizumab in multiple solid tumor types. Various biomarkers will be explored to enable a mechanistic understanding of clinical data and inform future trials. This study may also provide an opportunity to identify preliminary efficacy signals for IO-202 as a monotherapy and as a combination with a PD-1 inhibitor in patients with advanced solid tumors.

ABOUT LILRB4 (also known as ILT3)

LILRB4, also known as ILT3, is an immune inhibitory transmembrane receptor expressed by monocytic myeloid cells, including dendritic cells, monocytes, monocytic myeloid-derived suppressor cells and tumor-associated macrophages. LILRB4 inhibits antigen-presenting cell function, resulting in immune tolerance. LILRB4 is also expressed on certain hematologic cancer cells. Immune-Onc and The University of Texas published pioneering research in Nature illuminating the role of LILRB4 in immune suppression and tumor infiltration in acute myeloid leukemia (AML) and presented the rationale for targeting LILRB4 in solid tumors at the 2021 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting.

ABOUT IO-202

IO-202 is a first-in-class LILRB4 antagonist antibody with broad potential as an immunotherapy in both blood cancers and solid tumors. In hematologic malignancies, preclinical studies showed that IO-202 converts a "don’t kill me" to a "kill me" signal by activating T cell killing and converts a "don’t find me" to a "find me" signal by inhibiting infiltration of blood cancer cells. In the context of solid tumors, preclinical studies showed that IO-202 enhances dendritic cell function and T cell activation in vitro and inhibits tumor growth in an immune competent model in vivo.

IO-202 has two ongoing clinical studies: Its first Phase 1 trial is currently enrolling patients with acute myeloid leukemia (AML) or chronic myelomonocytic leukemia (CMML) as a monotherapy and in combination with azacitidine (NCT04372433). The U.S. Food and Drug Administration granted IO-202 Orphan Drug designation for treatment of AML in 2020 and Fast Track designation for relapsed or refractory AML in 2022. The second Phase 1 trial of IO-202 is currently enrolling patients with advanced solid tumors to evaluate IO-202 as a monotherapy and in combination with an anti-PD-1 (NCT05309187).