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.

On October 19, 2020 ONK Therapeutics Ltd, an innovative natural killer (NK) cell therapy company, reported that it has raised US$8M in a financing from new and existing investors (Press release, ONK Therapeutics, OCT 19, 2020, View Source [SID1234568612]). This brings the total raised in the last six months to US$14.6M. It also announces the appointment of Chris Nowers as Chief Executive Officer (CEO).

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The new financing round was led by New York-based investor Acorn Bioventures, and current shareholders, principally Seamus Mulligan, an experienced biopharmaceutical executive. The new investment will be used to expand the company’s team, its pre-clinical R&D and its manufacturing capabilities, in order to progress its novel, dual-targeted, natural killer (NK) cell therapy platform towards human clinical trials.

Founded in 2015, by Chief Scientific Officer (CSO) Prof. Michael O’Dwyer, ONK Therapeutics is a pre-clinical stage company dedicated to the development of a best-in-class, off-the-shelf, dual-targeted NK cell therapy platform, targeting solid and hematological cancers. This unique approach combines the expression of a chimeric antigen receptor (CAR) and a high affinity, membrane-bound TNF related apoptosis inducing ligand variant (TRAILv). This is coupled with a strong research focus on strategies to enhance homing and persistence as well as to overcome exhaustion, including the exploration of proprietary gene edits, such as the deletion of checkpoint inhibitory receptors in NK cells. The company is advancing an expanding portfolio of product candidates based on this unique platform.

Chris Nowers joins as CEO to lead the company’s expansion and development. Chris is an experienced biopharma executive, with significant cell therapy expertise from his tenure at both Kite Pharma (Head of Europe) and Cell Medica (CEO). Additional roles spanning more than 25 years in the biopharma industry include senior leadership positions as CEO of Avantogen Oncology, General Management roles at Amgen, and senior global and regional commercial leadership roles in the field of immunology at Bristol-Myers Squibb (BMS).

The company’s lead research program, ONKT101, is a dual-targeted NK cell therapy incorporating a CD19 CAR and TRAILv targeting the death receptor pathway (DR5) intended for the treatment of relapsed/refractory B cell malignancies. This program is partnered with Avectas and will utilize its proprietary SOLUPORETM technology as a means of non-viral genetic modification. The second program, ONKT102, combines an optimized affinity CD38 CAR and a TRAILv targeting DR5 intended for the treatment of patients with relapsed/refractory multiple myeloma.

Chris Nowers, CEO, said "I was attracted to the company’s innovative and unique approaches, which harness the natural biology of NK cells, and further optimize them through genetic modifications to improve both their cytotoxicity and functionality. This exciting off-the-shelf platform has the potential to produce a next-generation of cell therapies, which could improve performance and overcome some of the shortcomings seen with earlier approaches."

Commenting on the investment, Isaac Manke, PhD, Partner at Acorn Bioventures said "ONK Therapeutics is a highly innovative next-generation NK cell therapy company with an exciting portfolio of research stage assets targeting both hematological and solid tumors. It is anticipated that this financing will enable the company to progress multiple programs through IND enabling work and towards clinical studies."

Following the investment, Dr Manke and Mr Nowers will join the board of directors.

On October 19, 2020 Oncopeptides AB (publ) (Nasdaq Stockholm: ONCO) reported that the Company has submitted an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA), for OPD5 – a second drug candidate based on the proprietary Peptide Drug Conjugate platform (PDC) (Press release, Oncopeptides, OCT 19, 2020, View Source [SID1234568611]).

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Oncopeptides plans to initiate clinical development of OPD5 with an open-label phase 1, dose escalation study on safety and tolerability of OPD5 as a myeloablative regimen followed by Autologous Stem Cell Transplantation in patients with relapsed refractory multiple myeloma. The specific formulation enables administration of high doses which provides a clear rationale for treatment of this patient group

"This is an important milestone for Oncopeptides and enables us to further leverage the PDC-platform and develop a potential treatment for diseases where there is a significant unmet medical need", says Marty J Duvall, CEO of Oncopeptides AB. "We estimate to recruit the first patient in the phase 1 study in H1, 2021".

OPD5 is based on the proprietary PDC platform. Peptide-drug conjugates leverages aminopeptidases and releases alkylating agents rapidly into tumor cells. Aminopeptidases are overexpressed in tumor cells and are even more pronounced in advanced cancers and tumors with a high mutational burden. Thus, targeting aminopeptidases results in selective activity in cancer cells, sparing healthy cells which leads to a stronger benefit-to-risk profile.