On September 22, 2021 AB Science SA (Euronext – FR0010557264 – AB) reported that its clinical trial with AB8939 in adult patients with relapsed/refractory acute myeloid leukemia (AML) has been approved by Health Canada (Press release, AB Science, SEP 22, 2021, View Source [SID1234591053]). The ‘No Objection Letter’ (NOL) received from Health Canada provides an acknowledgement of AB8939’s drug candidacy and the authority to proceed with a Phase I/II study (AB18001) in patients with refractory and relapsed AML and refractory myelodysplastic syndrome (MDS) .

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AB8939 is a new generation synthetic microtubule destabilizer with the ability to overcome multidrug resistance and the potential for broad applicability as a potent anticancer drug. Microtubules play a crucial role in multiple cellular functions which makes them an important target for cancer therapy. Indeed, chemotherapies that target microtubules, such as taxanes and vinca alkaloids, are among the most successful anticancer therapeutics available. Unfortunately, the development of drug resistance (for example, via Pgp efflux pumps that transport the drugs out of the cancer cells) often restrict their clinical efficacy.

Key characteristics of AB8939 are that it circumvents difficulties associated with Pgp-dependent multidrug resistance and is not deactivated by an enzyme named myeloperoxidase, which is an advantage over existing chemotherapies. Another advantage and distinguishing characteristic of AB8939 is that it is a synthetic drug.

The therapeutic potential of AB8939 has been demonstrated through a series of preclinical experiments [1–3]. In vivo data from a highly resistant Ara-C patient derived xenograft (PDX) mouse model showed that AB8939, administered alone or in combination with Ara-C, increased survival relative to single agent Ara-C, with an accompanying significant reduction of blasts in blood and decrease in tumor growth [1]. Ara-C is considered the clinically most relevant cytotoxic drug for AML treatment. In another example, cancerous tumors from patients suffering from resistant acute megakaryoblastic leukemia (an AML subtype) were transplanted into mice. Data showed a complete response in mice treated with AB8939, as compared with rapid disease progression in control animals [2]. No apparent toxicity was observed during the time course of the treatment.

Based on these results, AB8939 was granted orphan drug designation for AML from the U.S. Food and Drug Administration (FDA) [4].

The first indication AB8939 is being developed for is acute myeloid leukemia (AML), a rapid proliferating hematological cancer that originates in the bone marrow and quickly moves into the blood. Cytarabine (Ara-C) is the current standard chemotherapy for AML treatment, however, drug resistance is a major limitation to successful therapy. AB8939 therefore has strong potential as a second or third-line treatment in AML patients who are unfit to receive intensive chemotherapy.

The advantageous mechanistic characteristics of AB8939 mean that it is potentially applicable to a large number of other oncology indications currently treated by microtubule-inhibitor drugs (such as taxanes and vinca alkaloids) and in particular hematological cancers. The envisioned strategy is to position AB8939 in patients with abnormal cytogenetics that make these patients unresponsive to first-line therapy.

Professor Olivier Hermine, President of the Scientific Committee of AB Science and member of the Académie des Sciences in France said, "We believe that AB8939 could represent a major breakthrough in the development of effective microtubule-targeting agents, an extensively used class of cancer treatment. Our preclinical data show that AB8939 exhibits broad anticancer activity, with a notable advantage of it being able to overcome common mechanisms of drug resistance. AB8939 therefore has strong potential to be developed in numerous oncology indications, with our initial targets being hematological cancers. We are excited about the start of this first AB8939 study in acute myeloid leukemia (AML), which represents a significant milestone in the clinical program of AB Science. AB8939 seems particularly well-suited for the treatment of relapsed or refractory AML, for which there are very limited therapeutic options."

AB8939 was entirely discovered by the laboratories of AB Science, which retains full ownership of intellectual rights, and is an example of AB Science’s focus on innovative drug development focused on improving patients’ lives.

About Study AB18001
Study AB18001, titled ‘A Phase 1/2 Study to Assess the Safety, Pharmacokinetics, and Efficacy of Daily Intravenous of AB8939 in patients with Relapsed/Refractory Acute Myeloid Leukemia’, has a multi-stage design. The first part is a dose escalation study that aims to determine the safety and tolerability of intravenous AB8939 in patients with refractory or relapsed AML or patients with refractory MDS, and to determine the recommended dose for the second-stage dose expansion study. This dose expansion study aims to determine the schedule for a Phase 2 trial in patients with relapsed/refractory AML and to also provide an early efficacy (response rate) assessment of AB8939.

About acute myeloid leukemia (AML)
Acute myeloid leukemia (AML) is a serious, life-threating condition and the most common cause of leukemia-related mortality, with a majority of patients facing a highly unsatisfactory prognosis. As such, AML represents an unmet medical need, with limited therapeutic options for patients who are refractory or too frail to benefit from potentially curative but highly toxic treatment, or for those patients that have relapsed following a first complete response. The prevalence of AML in western countries is around 1 per 5,000 persons [5], corresponding to around 100,000 cases in Europe and 60,000 in the USA. Among AML patients, it is estimated that approximately 50% of the patients will not have stem cell transplantation and will relapse. Therefore, the estimated targeted population of AB8938 in AML is around 80,000 people in Europe and the US.

References
[1] Goubard A, Humbert M, Mansfield C, Hermine O, Dubreuil P, et al. In Vivo Assessment of the Next Generation Microtubule-Destabilizing Agent AB8939 in Patient-derived Xenograft Models of Acute Myeloid Leukemia. Blood (2019) 134 (Supplement_1): 5142. doi.org/10.1182/blood-2019-127143

[2] Goubard A, Humbert M, Mansfield C, Hermine O, Dubreuil P, et al. AB8939, a Microtubule-Destabilizing
Agent with Potential to Overcome Multidrug Resistance, is Active Across the Range (M0–M7) of Acute Myeloid Leukemia Subtypes. Blood (2019) 134 (Supplement_1): 5154. doi.org/10.1182/blood-2019-127021

[3] Humbert M, Goubard A, Mansfield C, Hermine O, Dubreuil P, et al. Anticancer Activity of a Highly Potent Small Molecule Tubulin Polymerization Inhibitor, AB8939. Blood (2019) 134 (Supplement_1): 2075. doi.org/10.1182/blood-2019-122540

[4] Press release dated November 7, 2019

[5] National Cancer Institute (View Source)

On September 22, 2021 Immunocore Holdings Plc (Nasdaq: IMCR), a late-stage biotechnology company pioneering the development of a novel class of T cell receptor (TCR) bispecific immunotherapies designed to treat a broad range of diseases, including cancer, infection and autoimmune disease, reported that data from a phase 3 randomized trial comparing tebentafusp (IMCgp100) with investigator’s choice in first-line metastatic uveal melanoma (mUM) has been published in The New England Journal of Medicine (NEJM) (Press release, Immunocore, SEP 22, 2021, View Source [SID1234590905]).

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The paper concluded that tebentafusp is the first systemic treatment to show a survival benefit in mUM and should become a new treatment option for this poor prognosis disease.

"The publication of these phase 3 data in a leading peer-reviewed scientific publication like NEJM demonstrates the significance of Immunocore’s work in the field of TCR therapy," said Bahija Jallal, Chief Executive Officer of Immunocore. "This further validates the potential of tebentafusp to provide a much needed treatment option for patients with metastatic uveal melanoma, making a meaningful difference to patients’ lives. In addition, we believe these data show the broader potential of Immunocore’s TCR technology for the treatment of other solid tumors."

Results from the randomized, open-label, phase 3 trial of tebentafusp vs. investigator’s choice in previously untreated HLA-A*02:01-positive patients with mUM demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) as a first-line treatment in mUM. The OS Hazard Ratio (HR) in the intent-to-treat population favored tebentafusp, HR=0.51 (95% CI: 0.37, 0.71); p< 0.0001, over investigator’s choice (82% pembrolizumab; 12% ipilimumab; 6% dacarbazine). Treatment-related adverse events were manageable and consistent with the proposed mechanism.

Tebentafusp has been granted Breakthrough Therapy Designation, Fast Track designation and orphan drug designation by the U.S. Food and Drug Administration (FDA) and Promising Innovative Medicine (PIM) designation under the UK Early Access to Medicines Scheme for metastatic uveal melanoma. Immunocore’s biologics license application for approval of tebentafusp for the treatment of HLA-A*02:01-positive adult patients with metastatic uveal melanoma was recently accepted by the FDA. In addition, the European Medicine Agency (EMA)’s Committee for Medicinal Products for Human Use (CHMP) accepted Immunocore’s Marketing Authorisation Application (MAA).

On September 22, 2021 Cannabics Pharmaceuticals Inc. (OTCQB: CNBX), a global leader in the development of cancer related cannabinoid-based medicine, reported that the Company will present at the 4th Annual International Cannabinoid-Derived Pharmaceuticals Summit in Boston (Press release, Cannabics Pharmaceuticals, SEP 22, 2021, View Source [SID1234590540]). Our team will be participating along with others from across the cannabinoid research and drug development space, including industry and academic experts from major pharmaceutical companies, biotech firms, and world leading universities.

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Gabriel Yariv, company President and COO said: "The Cannabinoid Derived Pharmaceuticals Summit in Boston is the world largest conference exclusively devoted to CDP for medical conditions using FDA/EMA approval regularly pathways and with focus on clinical trials across the world and we are honored and proud to have been invited to participate at this 2021 4th Edition in Boston."

Eyal Barad, Cannabics Pharmaceuticals’ Co-founder and CEO commented: "The remarkable success of cannabinoids being approved today is just the beginning and we are excited to participate at the Cannabinoid Derived Pharmaceuticals Summit."

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Recent expansion of Cannabics Pharmaceuticals’ Board of Advisors to include: Prof. Caroline Robert (MD, Ph.D.), a Melanoma expert, and, Dr. Sigal Tavor (MD), a Hematology expert, along with Prof. Amos Toren (MD), Prof. Zamir Halpern (MD), Prof. Noam Shomron (Ph.D.), Dr. Erez Scapa (MD), Dr. Dana Ben-Ami Shor (MD), Dr. Sigalit Arieli-Portnoy (Ph.D.) and Dr. Tal Mofkadi (Ph.D.).

Recent expansion of Cannabics Pharmaceuticals’ Board of Directors to include: Dr. Inbar Maymon-Pomeranchik (Ph.D.), and Dr. Gil Feiler (Ph.D.) as Independent Directors.

On September 22, 2021 BiVictriX Therapeutics plc (AIM: BVX), an emerging biotechnology company applying a novel approach to develop next generation cancer therapies using insights derived from frontline clinical experience, reported the successful completion of two antibody discovery campaigns with IONTAS, aimed at supporting the optimisation of BiVictriX’s lead program, BVX001 (Press release, FairJourney Biologics, SEP 22, 2021, https://fjb.pt/collaboration/bivictrix-and-iontas-successfully-complete-two-antibody-discovery-campaigns/ [SID1234590246]).

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IONTAS, a leading clinical research organisation offering phage and next generation mammalian display antibody discovery services, has successfully identified novel human binders which target BiVictriX’s proprietary "twin cancer antigens", as part of an ongoing collaboration with BiVictriX. These binders cover a broad range of affinities including species cross-reactivity. They will be further assessed in-house by BiVictriX through in vitro characterisation and testing of all possible combinations of targets to validate the efficacy and selectivity in human cell models and further optimise lead program, BVX001.

BiVictriX is using a first-in-class approach to generate a proprietary pipeline of Bi-Cygni therapeutics which are designed to selectively target antigen co-expression fingerprints, or "twin antigens", on tumour cells, which are largely absent from healthy cells. BVX001, BiVictriX’s lead program, is in preclinical development for Acute Myeloid leukaemia, one of the most aggressive forms of blood cancer.

Tiffany Thorn, Chief Executive of BiVictriX Therapeutics plc, commented: "The delivery of these novel binders with species cross-reactivity is an important step for the team and our pipeline and a testament to our successful and ongoing collaboration with IONTAS. The team will begin validating these through in-house testing soon with the aim of determining the efficacy and specificity of the target affinity of each arm as we continue to develop our therapeutics."

António Parada, Chief Executive of IONTAS, added: "We’re delighted to have been able to support the development of BVX001 through our proprietary antibody discovery services. BiVictriX’s Bi-Cygni therapeutics, which target antigen co-expression fingerprints, or "twin antigens", on tumour cells look highly innovative and we wish the company every success as BVX001 progresses in preclinical development."

This announcement follows the recent appointment of Dr Oliver Schon as Vice President of Product Development and Chemistry Manufacturing and Controls and the Company’s successful listing on the London Stock Exchange’s AIM Market in August.

On September 22, 2021 The Coriell Institute for Medical Research and Van Andel Institute (VAI) reported that they have been awarded a prestigious Specialized Programs of Research Excellence (or SPORE) grant from the National Cancer Institute (award P50CA254897) (Press release, Van Andel Institute, SEP 22, 2021, View Source;utm_medium=rss&utm_campaign=spore-award-epigenetics-cancer-research [SID1234590242]). The five-year grant valued at an estimated $12.4 million will support nearly 20 scientists as they work to improve epigenetic therapies for cancer. The project is co-led by Coriell’s President and CEO Jean-Pierre Issa, M.D., Van Andel Institute’s Chief Scientific Officer Peter A. Jones, Ph.D., D.Sc. (hon), and Johns Hopkins University and VAI’s Stephen Baylin, M.D.

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NCI utilizes SPORE grants to empower interdisciplinary and collaborative research into specific aspects of cancer. This prestigious grant is the first of its kind at both Coriell and VAI, establishing them as premier institutions for cancer research. The award currently is the only SPORE grant awarded to an organization in New Jersey. This grant, which is also the first to support a thematic SPORE focused on epigenetics in NCI history, can be renewed indefinitely.

"SPORE grants hold a special place in translational cancer research. Through them, the NCI enables groundbreaking work and the trust it puts in the awarded scientists allows for unparalleled freedom and collaboration," said Dr. Issa. "It’s a true honor to receive this grant and it’s a sign of more exciting things to come for the Coriell Institute."

Jones, Baylin and Issa also collaborate on the Van Andel Institute (VAI)–Stand Up To Cancer (SU2C) Epigenetics Dream Team, which has launched more than a dozen epigenetic therapy clinical trials in recent years and will support trials from this SPORE. Jones and Baylin co-led both the first iteration of the SU2C Epigenetics Dream Team, which was established in 2009, and co-lead the current team, which was launched in 2014. Much of the SPORE project’s design was informed by SU2C’s collaborative model, which brings together experts and organizations to unite against cancer.

"Epigenetic therapies hold immense potential to shift the paradigm in cancer treatment," Dr. Jones said. "We’re thrilled to be recipients of a SPORE award, which is an exceptional mechanism for catalyzing collaboration and powering discovery."

Epigenetic therapy aims to treat cancer by correcting abnormal gene expression. In doing so, these therapies can also make other cancer therapies more effective. This SPORE seeks to improve on current epigenetic therapies by exploring new targets, investigating novel combinations of epigenetic therapies with other cancer treatments, and by designing, and running clinical trials to evaluate these promising strategies.

"Research in the last decade has reinforced the promise of epigenetic therapies both as a standalone treatment strategy and as a way to enhance existing approaches such as immunotherapy," Baylin said. "The SPORE award will allow us to investigate the underpinnings of epigenetics in cancer, with the goal of translating our findings to the clinic."
The three research projects in this SPORE include:

Project 1: A collaboration between the Coriell Institute and Hackensack Meridian School of Medicine led by Dr. Issa and Hackensack Meridian’s Yi Zhang, Ph.D., a member of the Hackensack Meridian Center for Discovery and Innovation and part of the Georgetown Lombardi Comprehensive Cancer Center. This group will investigate the potential of a certain group of kinases, enzymes that regulate proteins, as therapeutics targets.
Project 2: A collaboration between Baylin and VAI’s Scott Rothbart, Ph.D. This team will investigate a potentially novel therapeutic strategy for treating solid tumors by inhibiting DNMT and EZH1/2 enzymes.
Project 3: A collaboration between Indiana University’s Ken Nephew, Ph.D., and Kathy Miller, M.D., and University of Maryland School of Medicine’s Feyruz Rassool, Ph.D. This team will investigate the impact of epigenetic therapy on cancers driven by BRCAness, a major cancer-related vulnerability.
To aid these research projects, the SPORE grant also will support two shared scientific resource cores: A Genomics Core at Coriell Institute and a Pathology and Biorepository Core at VAI. Scientists working on these related research projects can utilize these resources in conducting their work.

Additionally, the SPORE will include the creation of a Career Enhancement Program and a Developmental Research Program, which provide research awards to faculty (inside and outside of the SPORE group) to support recruitment and retention of scientists with a focus of bolstering diversity in the field.

Dr. Issa is also currently an investigator on The Joe Moakley Leukemia SPORE, a program supported by a SPORE grant administered out of The University of Texas MD Anderson Cancer Center. That grant is in its 18th year.