On October 7, 2021 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 that clinical data on MCLA-158, including clinical responses observed in advanced head and neck squamous cell carcinoma (HNSCC) and preclinical data on zenocutuzumab (Zeno) at the AACR (Free AACR Whitepaper)-NCI-EORTC Virtual AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) (Press release, Merus, OCT 7, 2021, View Source [SID1234590973]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Dr. Andrew Joe, Chief Medical Officer at Merus, said, "We are encouraged by the early evidence of clinical activity of MCLA-158 in patients with advanced, previously treated HNSCC, further validating the potential of our Biclonics platform. With Zeno, our preclinical research continues to reinforce the mechanisms by which Zeno is capable of potently inhibiting the growth of NRG1 fusion cancers."

MCLA-158 (petosemtamab)
The reported data are from the ongoing phase 1 dose expansion cohort that is investigating the safety, tolerability, and anti-tumor activity of MCLA-158 monotherapy in advanced HNSCC.

Observations in the presentation include:

Enrollment of 10 patients with advanced HNSCC, as of the safety and efficacy data cutoff date of August 9, 2021, with median age of 65 (range 50-77) years, and who were treated with a median of 2 lines of prior therapy.
Seven patients were evaluable for an interim efficacy analysis by investigator assessment (three patients were enrolled <8 weeks from the cutoff date).
Three of seven patients achieved partial responses, with one achieving complete response after the data cutoff date. Tumor reduction was observed in all seven patients.
The safety profile of MCLA-158 was based on 29 patients with advanced solid tumors who were treated at 1500 mg every two weeks across the phase 1 trial.
The most frequent adverse events (AEs) were infusion related reactions; 72% any grade, 7% grade ≥ 3.
Mild to moderate skin toxicity (3% grade ≥3).
The Company is planning its next update on the MCLA-158 trial in 2022.

Zeno
Observations in the preclinical presentation include:

The bispecific HER2/HER3 antibody Zeno blocked cell growth 100 fold more potently than the bivalent HER3 antibody derived from Zeno, in an NRG1 driven growth assay.
Zeno potently blocked NRG1-fusion mediated downstream signaling and growth in vitro and in vivo.
Zeno induced both antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) mediated killing of cancer cells in a dose-dependent manner.
As of September 1, 2021 more than 80 patients with NRG1 fusion cancers have been treated with Zeno monotherapy in our phase 1/2 eNRGy trial and Early Access Program. (www.nrg1.com).
About MCLA-158
MCLA-158, or petosemtamab, is an ADCC-enhanced human IgG1 Biclonics designed to bind to cancer stem cells (CSCs) expressing leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) and epidermal growth factor receptor (EGFR). In preclinical models, MCLA-158 binding triggers EGFR degradation in LGR5+ CSCs and is designed to have two different mechanisms of action. The first entails blocking of growth and survival pathways in cancer initiating cells. The second exploits the recruitment and enhancement of immune effector cells to directly kill cancer initiating cells that persist in solid tumors and can cause relapse and metastasis.

About Zeno
Zeno is an antibody-dependent cell-mediated cytotoxicity (ADCC)-enhanced Biclonics that utilizes the Merus Dock & Block mechanism to inhibit the neuregulin/HER3 tumor-signaling pathway in solid tumors with NRG1 gene fusions (NRG1+). Through its unique mechanism of binding to HER2 and potently blocking the interaction of HER3 with its ligand NRG1 or NRG1-fusion proteins, Zeno has the potential to be particularly effective against NRG1+ cancers. In preclinical studies, Zeno also potently inhibits HER2/HER3 heterodimer formation and tumor growth in models harboring NRG1 fusions.

On October 7, 2021 Apollo Endosurgery, Inc. ("Apollo") (NASDAQ:APEN), a global leader in less invasive medical devices for gastrointestinal and bariatric procedures, reported that preliminary unaudited financial results and corporate updates for the third quarter ended September 30, 2021, including anticipated revenue in the range of $16.0 million to $16.4 million and anticipated revenue growth in the range of 25% to 28% compared to third quarter 2020 (Press release, Apollo Endosurgery, OCT 7, 2021, View Source [SID1234591010]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Preliminary, Unaudited Third Quarter 2021 Financial Results

"We continue to successfully deliver against the priorities that we committed to early this year: specifically, to energize our business and drive near-term growth while laying the foundation for additional large-scale opportunities," said Chas McKhann, president and CEO. "Our recent De Novo 510(k) classification request for Apollo ESG and Apollo REVISE is an important, critical milestone for the company, and I am extremely proud of the work our clinical and regulatory teams have done to get us to this point. We believe we are well-positioned to become a leader in therapeutic endoscopy through continued execution on both our commercial and clinical initiatives. I’m excited about the bright future ahead for Apollo."

Anticipated revenue growth in the third quarter was led by the company’s endoscopic suturing (ESS) portfolio, which grew between 31% and 33% over the same period in 2020, highlighting continued demand for Apollo’s OverStitch and X-Tack products across a range of patient indications. Anticipated intragastric balloon (IGB) revenue increased by 19% to 21% despite a stronger-than-expected rebound in elective procedures for the ORBERA balloon in the prior year third quarter.

Apollo estimates that it had approximately $28 million in cash, cash equivalents, and restricted cash at September 30, 2021.

The company expects to announce third quarter final financial and operating results on November 1, 2021, after market close.

De Novo 510(k) Classification Request Submitted for Apollo ESG and Apollo REVISE

Apollo announced that it has submitted a De Novo classification request to the U.S. Food and Drug Administration (FDA) seeking 510(k) classification and clearance for the Apollo ESG and Apollo REVISE devices, which consist of the OverStitch Endoscopic Suturing System and related components (e.g., tissue helix, sutures, cinches). Apollo ESG is intended for use in the endoscopic sleeve gastroplasty procedure for weight loss and Apollo REVISE is intended for use in revision of bariatric surgery procedures. This submission follows recent announcements made during the Surgical Disruptive Technologies Summit by the principal investigators of the MERIT study (Multi-Center ESG Randomized Interventional Trial), that, based upon a preliminary analysis, the trial had met its primary endpoints for safety and efficacy.

The De Novo Classification Process is available to medical devices of low-to-moderate risk that do not have a legally marketed predicate device. Actual timing for the De Novo 510(k) process varies. The company currently expects a decision from the FDA within approximately 12 months.

2021 Financial Outlook

Based on results in the first three quarters of 2021, the company is updating its revenue guidance for the full year 2021 to between $63 and $64 million, which represents growth of 50% to 52% over 2020.

Apollo continues to monitor the potential and uncertain impact of the ongoing COVID-19 pandemic. Should hospitals or outpatient centers where the company’s procedures are performed experience continued or additional surges in cases and need to defer elective procedures to preserve capacity for COVID-19 patients, the company’s ability to achieve these financial projections could be adversely affected.

About the MERIT Study

The MERIT study (NCT03406975, FDA IDE G190189) is a multi-center, prospective randomized clinical trial evaluating the safety and effectiveness of the ESG procedure, a minimally invasive, endoscopic weight loss procedure performed with Apollo Endosurgery’s OverStitch Endoscopic Suturing System compared to a medically monitored regimen of diet and healthy lifestyle. The co-principal investigators are Dr. Erik Wilson, University of Texas at Houston (Houston, TX), and Dr. Barham Abu Dayyeh, Mayo Clinic, (Rochester, MN) under a collaborative research agreement sponsored by Apollo Endosurgery. The study’s primary efficacy endpoint is to achieve at least 25% excess body weight loss (%EBWL) at 12 months and at least 15% EBWL vs. control at 12 months, and the primary safety endpoint is a serious adverse event rate of less than 5%. Additionally, patients undergoing ESG are being evaluated for improvement in hypertension and type 2 diabetes at 24 months.

The MERIT study investigators submitted an abstract to the International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO). The company anticipates that the MERIT investigators will present the study’s primary efficacy and safety endpoints in a global, virtual session entitled the "Top 10 Papers at IFSO" on Friday, October 22, 2021. The company anticipates that the full MERIT study results, including patient follow-up to two years, will be published in the first half of 2022.

On October 7, 2021 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported multiple presentations, including initial clinical data from an ongoing Phase 1b study evaluating ORIC-101, a glucocorticoid receptor antagonist, in combination with enzalutamide, in patients with metastatic prostate cancer progressing on enzalutamide (Press release, ORIC Pharmaceuticals, OCT 7, 2021, View Source [SID1234590917]). The abstracts and presentations are available for on-demand viewing via the online platform for AACR (Free AACR Whitepaper)-NCI-EORTC as of October 7, 2021, at 9 a.m. ET.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Presentations:

Initial results from a Phase 1b study of ORIC-101, a glucocorticoid receptor antagonist, in combination with enzalutamide in patients with metastatic prostate cancer
Biomarker results supporting selection of RP2D from a Phase 1b study of ORIC-101, a glucocorticoid receptor antagonist, in combination with enzalutamide in patients with metastatic prostate cancer progressing on enzalutamide
ORIC-114, an orally bioavailable, irreversible kinase inhibitor, has superior brain penetrant properties and enhanced potency in preclinical studies of HER2-positive breast cancer
"We are pleased to share initial data from our ORIC-101 clinical program in patients with metastatic prostate cancer. The combination was well tolerated without evidence of drug-drug interaction affecting enzalutamide dosing and has demonstrated preliminary evidence of antitumor activity in the relevant patient population," said Pratik S. Multani, MD, chief medical officer. "Given the tumor heterogeneity in metastatic prostate cancer, we’ve made significant progress in identifying a key patient population that may benefit from ORIC-101 and, within these patients, seen preliminary evidence of more pronounced clinical benefit in patients whose tumors express higher GR levels. Patients are continuing to enroll in the expansion cohort and we look forward to reporting an update from the Phase 1b trial in 2022."

ORIC-101: Glucocorticoid Receptor (GR) Antagonist

The Phase 1b clinical trial of ORIC-101 in combination with enzalutamide is a single arm, multicenter, open-label study conducted in two parts, intended to establish the recommended Phase 2 dose (RP2D), safety, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity when administered in patients with metastatic prostate cancer progressing on enzalutamide.

In the Part I dose escalation portion of the trial, three cohorts of patients were enrolled to evaluate daily dosing of ORIC-101 with doses ranging from 80 to 240 mg, in combination with 160 mg of enzalutamide once daily dosing. Following the completion of the dose escalation portion of the study, the RP2D was determined to be 240 mg of ORIC-101 and 160 mg of enzalutamide once daily.

In the Part II dose expansion portion of the trial, up to 48 patients with metastatic prostate cancer progressing on enzalutamide are expected to be enrolled and treated with the combination at the RP2D. Patients are enrolled independent of GR status, with retrospective analysis of GR expression and other potentially predictive biomarkers. Enrollment continues in the Part II dose expansion cohorts at nine clinical sites across the United States.

As of the August 20, 2021, data cut-off date:

Preliminary Safety Analyses:

25 patients were enrolled across Parts I/II of the study, which included 7 patients treated at non-RP2D doses and 18 patients treated at the RP2D of 240 mg of ORIC-101 and 160 mg of enzalutamide once daily.
RP2D was well tolerated; treatment-related adverse events were primarily Grade 1 or 2, with only four Grade 3 events, which all resolved with dose interruption.
Tolerability profile for the combination was generally consistent with that of single agent enzalutamide.
Preliminary PK Analysis:

Plasma concentrations exceeded the threshold for GR inhibition at all dose levels.
ORIC-101 exposure increased with dose.
No evidence observed of drug-drug interaction impacting enzalutamide levels.
Preliminary Biomarker Analyses:

GR pathway suppression, evaluated using GR target gene expression, was observed after one dose of ORIC-101 in peripheral blood mononuclear cells from 22 of 23 patients.
Moderate to high GR expression (IHC H-score ≥ 100) in prostate tumor cells was observed in 76% of pretreatment biopsies.
Translational efforts identified a key patient population, in line with published literature, consisting of the ~60% of patients with tumors lacking biomarkers of AR resistance (e.g., ARv7 splice variant, AR L702H point mutation) and AR independence (e.g., lineage switching).
Preliminary Antitumor Activity:

Within the key patient population (n=8), 75% (6 of 8) of patients’ tumors expressed moderate to high GR and 25% (2 of 8) of patients’ tumors expressed low GR.
The two patients with low GR came off treatment at less than two months. In contrast, the six patients with moderate to high GR demonstrated prolonged time on treatment (with two patients on treatment for over seven months, and another four patients still ongoing at varying durations at the time of the data cut).
ORIC-101 is also being evaluated in a Phase 1b trial in combination with nab-paclitaxel in up to 132 patients across four cohorts, including pancreatic ductal adenocarcinoma, ovarian cancer, triple negative breast cancer, and other advanced solid tumors. Enrollment continues in this study at 12 clinical sites across the United States and an additional update is expected in 2022.

ORIC-114: EGFR/HER2 Inhibitor

ORIC-114 is a brain penetrant, orally bioavailable, irreversible inhibitor designed to selectively target EGFR and HER2 with high potency against exon 20 insertion mutations. These are the first publicly disclosed preclinical data with ORIC-114 demonstrating compelling activity in HER2-positive breast cancer models.

Key Findings of the Presentation:

ORIC-114 demonstrated greater cell potency on HER2-positive breast cancer cell lines relative to non-amplified cell lines and was more potent than lapatinib and tucatinib, two approved tyrosine kinase inhibitors for the treatment of HER2-positive breast cancer.
ORIC-114 demonstrated robust tumor regressions in a HER2-positive breast cancer in vivo model without significant body weight loss.
ORIC-114 demonstrated superior brain exposure compared to other EGFR exon 20 and HER2 targeted agents.
Separately, today the company disclosed head to head in vivo preclinical data in an EGFR exon 20 NSCLC xenograft model demonstrating good tolerability and improved efficacy, including a 90% complete response rate, versus multiple clinical stage exon 20 inhibitors.

Webcast and Conference Call

ORIC will host a conference call and webcast today at 9:00 a.m. ET. To participate in the conference call, please dial (833) 651-0991 (domestic) or (918) 922-6080 (international) and refer to conference ID 3575856. A live webcast and audio archive of the conference call will be available through the investor section of the company’s website at www.oricpharma.com. The webcast will be available for replay for 90 days following the presentation.

About ORIC-101

ORIC-101 is a potent and selective small molecule antagonist of the glucocorticoid receptor, which has been linked to resistance to multiple classes of cancer therapeutics across a variety of solid tumors. Preclinical in vitro and in vivo data suggest ORIC-101 is able to address key resistance mechanisms of multiple classes of cancer treatments, including taxanes and androgen receptor modulators. Based on preclinical and clinical studies, ORIC-101 is expected to have reduced drug-drug interaction liabilities than other glucocorticoid receptor antagonists. Currently, there are no glucocorticoid receptor antagonists approved by the FDA for the treatment of cancer. Following the successful completion of two Phase 1a trials in over 50 healthy volunteers, ORIC initiated two separate Phase 1b trials of ORIC-101 in combination with (1) Abraxane (nab-paclitaxel) in advanced or metastatic solid tumors and (2) Xtandi (enzalutamide) in metastatic prostate cancer.

On October 7, 2021 IMMUNOPRECISE ANTIBODIES LTD. (the "Company" or "IPA") (NASDAQ: IPA) (TSX VENTURE: IPA) and the Pierre Fabre pharmaceutical group reported that IPA’s subsidiary, Talem Therapeutics LLC ("Talem"), and Pierre Fabre have entered a multi-year, multi-target research collaboration with the goal to discover and develop therapeutics antibodies for up to nine targets (Press release, ImmunoPrecise Antibodies, OCT 7, 2021, View Source [SID1234590933]). This strategic collaboration is expected to help expand Talem’s portfolio of novel antibodies across oncology. It adds to the variety of diverse relationships that the IPA group of companies holds across the pharmaceutical and biotechnology sector.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Under the research collaboration, scientists from both companies will work together and contribute their respective resources to discover and develop novel antibodies leveraging the IPA group’s antibody discovery technologies, such as B cell Select or Deep Display using wild-type and/or transgenic animals, available human libraries, as well as their signature "end-to-end" services. The antibodies developed in the research collaboration against the selected targets will be jointly owned by Talem and Pierre Fabre and, following the completion of each target specific research program, Pierre Fabre will have an option to obtain an exclusive worldwide license to Talem’s interest in those jointly discovered antibodies against that particular target, and Talem would be eligible to receive certain up-front and contingent downstream payments. In addition, if licensed, Pierre Fabre will be responsible for the preclinical and clinical development, as well as the commercialization of the jointly discovered antibodies.

"Less than two years ago we started Talem Therapeutics to provide a unique partnering opportunity for companies to jointly seek the development of promising novel candidates," stated Dr. Stefan Lang, Chief Business Officer of ImmunoPrecise. "We are very excited to join forces with Pierre Fabre, combining our advanced antibody technologies with their world-class expertise in immuno-oncology is a powerful strategic combination enabling the teams to jointly address life threatening human diseases."
"Drug discovery in immuno-oncology is a priority for Pierre Fabre. We are therefore very pleased to enter this multi-target research collaboration. Talem will provide us with its expertise and a variety of technology platforms to enable the discovery of therapeutic antibodies, towards a set of structurally diverse targets." added Francesco Hofmann, Head of R&D at Pierre Fabre Medical Care.

On October 7, 2021 -Gennao Bio, a privately-held genetic medicines company developing first-in-class, targeted nucleic acid therapeutics, reported new preclinical data for its gene monoclonal antibody (GMAB) platform technology was presented as a virtual poster presentation at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) (Press release, Gennao Bio, OCT 7, 2021, View Source [SID1234590950]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The results presented demonstrate GMAB’s ability to systemically target and deliver an RNA payload to central nervous system (CNS) tumors in a mouse model of human medulloblastoma (DAOY). Studies conducted with fluorescently labeled GMAB show that the antibody readily penetrates into the central nervous system, and is quickly internalized and retained by tumors. Additional studies combining GMAB with 3p-hpRNA, a known activator of the immune signaling RIG-I pathway, show more than 50% reduction in intracranial tumor burden and suppression of spinal metastases following a single dose.

"The results presented today further reinforce the potential of our GMAB platform in oncology and support continued advancement. We look forward to nominating our first clinical program by the end of the year," said Stephen Squinto, Ph.D., chief executive officer and chair of the board of Gennao Bio.

"Treating CNS tumors systemically is challenging given the need to cross the blood-brain barrier and often requires the use of complicated formulations and invasive methods of delivery," said Peter M. Glazer, M.D., Ph.D., Chair of the Department of Therapeutic Radiology, Professor of Genetics and Robert E. Hunter Professor of Therapeutic Radiology at the Yale School of Medicine. "These promising results highlight a novel, non-invasive, targeted approach for the systemic delivery of immunostimulatory RNAs to multiple tumors, offering the potential for improved treatments options over current approaches."

The full abstract and poster presentation can be accessed on the AACR (Free AACR Whitepaper)-NCI-EORTC conference website.