On October 19, 2020 Mereo BioPharma Group plc (NASDAQ: MREO, AIM: MPH) ("Mereo" or "the Company"), a clinical stage biopharmaceutical company focused on oncology and rare diseases, reported that the U.S. Food and Drug Administration has cleared an investigational new drug (IND) application to proceed with a Phase 1b/2 study for the Company’s lead oncology product candidate etigilimab (Press release, Mereo BioPharma, OCT 19, 2020, View Source [SID1234568624]). Etigilimab is a novel IgG1 monoclonal antibody against TIGIT (T-cell immunoreceptor with Ig and ITIM domains), a next generation checkpoint receptor shown to block T-cell activation and the body’s natural anti-cancer immune response.

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Mereo is on track to initiate the Phase 1b/2 basket study in the fourth quarter of 2020. The study will evaluate etigilimab in combination with an anti-PD-1 initially in approximately 100 patients with a defined series of tumor types, including biomarker enriched and rare tumor cohorts. The study will incorporate flat dosing (for patients 50 kg and higher) which is based on data from Mereo’s previous Phase 1a and Phase 1b combination studies with etigilimab.

Dr. John Lewicki, Chief Scientific Officer of Mereo, said: "Recent clinical data regarding anti-TIGIT therapies in combination with PDL-1/PD-1 inhibition have been promising. We designed etigilimab as a novel IgG1 which blocks TIGIT signalling while retaining an intact effector function and we believe our development approach is differentiated. We have selected the tumor types for our planned Phase 1b/2 basket combination study based on biomarker screening of large collections of different tumor samples and correlating these with suboptimal responses to anti- PDL-1/PD-1. We’ve also included tumor types where we saw evidence of activity in our previous Phase 1a/1b study. We look forward to initiating the study this quarter and providing additional details during our planned virtual R&D day."

In November 2020, Mereo plans to host a virtual R&D day featuring external experts to review the etigilimab development program, including the design and biomarker strategy of the Phase 1b/2 basket combination study. Mereo also plans to provide an overview of its rare disease product pipeline. Further information including the date/time of the virtual R&D day will be announced in the coming weeks.

About Etigilimab

Etigilimab is an antibody against TIGIT (T-cell immunoreceptor with Ig and ITIM domains). TIGIT is a next generation checkpoint receptor shown to block T-cell activation and the body’s natural anti-cancer immune response. Etigilimab is an IgG1 monoclonal antibody which binds to the human TIGIT receptor on immune cells with a goal of improving the activation and effectiveness of T-cell and NK cell anti-tumor activity. Mereo completed a Phase 1a dose escalation clinical trial with etigilimab in patients with advanced solid tumors and enrolled patients in a Phase 1b study in combination with nivolumab in selected tumor types.

23 patients were treated in the Phase 1a dose escalation study with doses up to 20 mg/kg Q2W. Tumor types included colorectal cancer, endometrial cancer, pancreatic cancer and other tumors. No dose limiting toxicities were observed. In the Phase 1b combination study, a total of ten patients, nine of whom had progressed on prior anti-PD-1/PD-L1 therapies were enrolled at doses of 3, 10, and 20 mg/kg. Eight patients were evaluable for tumor growth assessment, and all of these patients had progressed on PD-1/PD-L1 therapies with best responses including one patient with a partial response another with stable disease. These patients remained on study for up to 224 days. No dose limiting toxicities (DLTs) were observed and the most common related adverse events included fatigue, rash, and pruritis.

Mereo plans to initiate a Phase 1b/2 study of etigilimab in combination with an anti-PD-1 in a series of tumor types in Q4 2020.

On October 19, 2020 Scholar Rock(NASDAQ: SRRK), a clinical-stage biopharmaceutical company focused on the treatment of serious diseases in which protein growth factors play a fundamental role, reported the closing of a $50 million debt facility with Silicon Valley Bank and Oxford Finance LLC, of which the first $25 million was funded at closing (Press release, Scholar Rock, OCT 19, 2020, View Source [SID1234568623]). Scholar Rock intends to use the proceeds for general corporate purposes, including the advancement of the Company’s pipeline and for pre-commercialization preparations.

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"This non-dilutive financing strengthens Scholar Rock’s balance sheet as we advance our clinical programs and overall platform for patients affected by a wide range of serious diseases, including neuromuscular disorders, cancer, fibrosis, and anemia," said Ted Myles, CFO & Head of Business Operations of Scholar Rock. "Importantly, this facility provides added financial and operational flexibility as we head into important clinical read-outs for SRK-015 in spinal muscular atrophy and SRK-181 in immuno-oncology."

Scholar Rock’s approach to discovering and developing growth factor targeted drugs is fundamentally new and different from traditional approaches," stated Christopher A. Herr, Senior Managing Director at Oxford Finance. "As the company looks towards potential late-stage development with upcoming clinical data, we are pleased to provide capital to support their vision of developing novel medicines."

"Scholar Rock is an innovative biopharma company that is developing treatments for an array of diseases with high unmet medical needs and we are excited to expand our relationship to support their next phase of growth," said Kate Walsh, Director of Life Science and Healthcare at Silicon Valley Bank.

Under the terms of the debt facility, the second $25 million tranche is available through December 31, 2021 upon dosing of the first patient in a Phase 3 trial for SRK-015 and dosing of the first patient in Part B of the DRAGON Phase 1 trial for SRK-181. The debt facility will mature on May 1, 2025 and requires interest only payments for the first two years.

On October 19, 2020 Midatech Pharma PLC (AIM: MTPH.L; Nasdaq: MTP), an R&D biotechnology company focused on improving the bio-delivery and biodistribution of medicines reported encouraging headline results from a Phase I study at the University of California, San Francisco ("UCSF") in patients with Diffuse Intrinsic Pontine Glioma ("DIPG") (the "UCSF study" NCT03566199) (Press release, Midatech Pharma, OCT 19, 2020, View Source [SID1234568622]).

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The primary endpoint of the study was to determine the dosage regimen to be used in a proposed Phase II study of the safety and efficacy of MTX110 in patients with DIPG. Preliminary high-level data from the UCSF study supports a dose of between 60μM and 90μM of MTX110, depending upon patient tolerance over the course of 12 infusions in Phase II.

In total, seven patients were recruited into the UCSF study. Patients were newly diagnosed with DIPG and received focal external beam radiation therapy four to 14 weeks before commencement of MTX110 treatment. Eligibility required a pontine location of the tumour with diffuse involvement of at least two thirds of the pons and no evidence of metastatic disease. Patients were not excluded by total tumour volume. MTX110 was administered directly into the tumour via a micro-catheter using convection enhanced delivery ("CED") with gadolinium-enhanced intra-operative MRI to guide and track drug distribution to the tumour. Patients could receive up to 12 cycles of treatment every four to eight weeks. The dose was escalated between and within patients as tolerated initially by increasing the infusion volume at a concentration of 30μM MTX110 and then with higher drug concentrations of 60μM and 90μM as the sixth and seventh dose increments, respectively.

At the interim cut-off date (30 September 2020), median overall survival based on Kaplan Meier analysis was 26.06 months (CI 11.3 – 26.06 months) and overall survival at 12 months (OS12) was 71.4% (five of seven patients alive). Three patients remain alive and continue to be monitored. Survival was not an endpoint of the UCSF study nor was the study powered for statistical significance and therefore no conclusions as to the impact of MTX110 on overall survival rates can be drawn from these data.

The proposed Phase II trial is expected to evaluate overall survival at 12 months as the primary endpoint in 19 evaluable patients. The planned design is single arm and statistically powered for comparisons with defined historical survival data. MTX110 is expected to be delivered using an alternative CED catheter system that enables regular drug infusions directly into the tumour without a need for repeated surgery.

DIPG is a primary brain tumour arising in the pons (middle) of the brain stem, is diffusely infiltrating and cannot be surgically removed. Occurring mostly in children, the median survival rate in a cohort of 316 cases was 10.0 months and OS12 was 35% (Jansen et al, 2015. Neuro-Oncology 17(1):160-166). Although radiotherapy prolongs survival, the majority of patients die within one year following diagnosis. Systemic chemotherapy is ineffective, often due to an inability of agents to cross the blood-brain barrier. Approximately 1,000 (data on file) individuals are diagnosed with DIPG worldwide each year.

Commenting Sabine Mueller MD PhD, Principal Investigator of the UCSF study, said: "The study has determined a proposed dose range for MTX110 for Phase II and has shown that repeated delivery of MTX110 via CED is feasible and safe. In an upcoming Phase II study efficacy in this patient population will be assessed."

Commenting further, Steve Damment, EVP R&D of Midatech, said: "DIPG is a devastating pediatric brain cancer with limited treatment options and very poor outcomes. The overall survival data from this Phase I study are encouraging, although further study of MTX110 in DIPG is required to establish whether it can make a difference to these patients and their families."

Online Q&A Session

Stephen Stamp (CEO and CFO) and Steve Damment (EVP R&D) will be hosting an online Q&A session regarding this latest development at 2.00 p.m. London time / 9.00 a.m. US East Coast time on Monday 19 October 2020. This session is open to all existing and prospective shareholders. Those who wish to attend should register via:

View Source where they will be provided with access details. Participants will have the opportunity to ask questions during the session, but questions may also be submitted in advance to : [email protected]

About MTX110

MTX110 is a water-soluble form of panobinostat free base, achieved through complexation with hydroxypropyl-β-cyclodextrin (HPBCD), that enables convection-enhanced delivery (CED) at potentially chemotherapeutic doses directly to the site of the tumour. Panobinostat is a hydroxamic acid and acts as a non-selective histone deacetylase inhibitor (pan-HDAC inhibitor). The currently available oral formulation of panobinostat lactate (Farydak) is not suitable for treatment of brain cancers owing to poor blood-brain barrier penetration and inadequate brain drug concentrations. Based on favourable translational science data, MTX110 is being evaluated clinically as a treatment for DIPG (NCT03566199, NCT04264143) and recurrent medulloblastoma (NCT04315064), and preclinically for treatment of glioblastoma (SNO 2020 Abstract TMOD-27). MTX110 is delivered directly into and around the patient’s tumour via a catheter system (e.g. CED or fourth ventricle infusions) to bypass the blood-brain barrier. This technique exposes the tumour to very high drug concentrations while simultaneously minimising systemic drug levels and the potential for toxicity and other side effects. Panobinostat has demonstrated high potency against DIPG tumour cells in in vitro and in vivo models, and in a key study it was the most promising of 83 anticancer agents tested in 14 patient-derived DIPG cell lines (Grasso et al, 2015. Nature Medicine 21(6), 555-559).

On October 19, 2020 Selvita reported that it will participate in the upcoming 26th annual BIO-Europe global life sciences partnering event that will be held October 26–29 in a fully digital format (Press release, Selvita, OCT 19, 2020, View Source;utm_medium=rss&utm_campaign=selvita-will-participate-in-the-upcoming-26th-annual-bio-europe [SID1234568618]).

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Selvita’s digital company presentation will be available to all participants throughout the whole event in the ‘Pitch Room’. To schedule a one-on-one meeting with Selvita representatives, please contact us at [email protected]. We look forward to participating in virtual partnering meetings, on-line panel sessions, and the virtual exhibit.

Additional information is available on the conference website at https://informaconnect.com/bioeurope/

On October 19, 2020 Aptose Biosciences Inc. ("Aptose" or the "Company") (NASDAQ: APTO, TSX: APS), a clinical-stage company developing highly differentiated agents that target the underlying mechanisms of cancer, reported dosing of the first patient with acute myeloid leukemia (AML) in a Phase 1 a/b clinical study with CG-806, the company’s oral kinase inhibitor that potently inhibits the wildtype and mutant forms of FLT3 and BTK, and suppresses select clusters of kinases that drive oncogenic signaling pathways (Press release, Aptose Biosciences, OCT 19, 2020, View Source [SID1234568615]). The investigational drug is the only known clinical agent that potently inhibits both FLT3 and BTK, giving it broad therapeutic potential across the spectrum of lymphoid and myeloid hematologic malignancies.

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"We diligently and thoughtfully prepared for this trial," said William G. Rice, Ph.D., Chairman, President and Chief Executive Officer, "and we are grateful for the opportunity to treat relapsed or refractory AML patients with CG-806. The 450mg starting dose in AML patients was selected because that dose, when administered to CLL patients being treated in a separate Phase 1 a/b trial, appeared safe, well tolerated and achieved plasma exposure levels that effectively inhibited phospho-FLT3 activity, which is a key driver of AML."

Several clinical sites are screening patients for the Phase 1 a/b multicenter, open-label, dose escalation study of safety, pharmacodynamics, and pharmacokinetics of CG-806 in ascending cohorts (3+3 design) to determine the maximum tolerated dose or recommended dose in patients with relapsed or refractory AML.

Separate from the AML trial, Aptose is conducting a Phase 1 a/b dose escalation study with CG-806 in patients with B-cell malignancies, including chronic lymphocytic leukemia (CLL) and non-Hodgkin’s lymphomas (NHL), who have failed or are intolerant to current therapies.

About AML

Acute myeloid leukemia, or AML, is a heterogeneous and aggressive cancer of the bone marrow and blood that occurs in people of all ages, but is most common in adults older than 65. The American Cancer Society estimates this year that 19,940 people of all ages (11,090 men and boys and 8,850 women and girls) in the United States will be diagnosed with AML. AML has a poor prognosis and overall 5-year survival rate in adults of little more than 25 percent (for people younger than 20, the survival rate is 67 percent). Despite recent advances in the targeted treatment of AML, the majority of patients will relapse or remain refractory to current therapies and there remains a significant unmet need for new therapies.

About CG-806

CG-806 is an oral, first-in-class FLT3 and BTK cluster selective kinase inhibitor and is in Phase 1 clinical studies for the treatment of lymphoid and myeloid hematologic malignancies. This small molecule demonstrates potent inhibition of wild type and all mutant forms of FLT3 (including internal tandem duplication, or ITD, and mutations of the receptor tyrosine kinase domain and gatekeeper region), cures animals of AML in the absence of toxicity in murine leukemia models, and represents a potential best-in-class therapeutic for patients with AML and other myeloid malignancies. Likewise, CG-806 demonstrates potent, non-covalent inhibition of the wild type and Cys481Ser (C481S) mutant forms of the BTK enzyme, as well as other oncogenic kinase pathways operative in B cell malignancies, suggesting CG-806 may be developed for various B cell malignancy patients (including CLL/SLL, FL, MCL, DLBCL and others) that are resistant/refractory/intolerant to covalent or other non-covalent BTK inhibitors. Because CG-806 targets key kinases/pathways operative in malignancies derived from the bone marrow, it is in development for B-cell cancers and AML.