On April 8, 2021 Repare Therapeutics Inc. ("Repare" or the "Company") (Nasdaq: RPTX), a leading clinical-stage precision oncology company enabled by its proprietary synthetic lethality approach to the discovery and development of novel therapeutics, reported that it will host a virtual Investor Day webcast today from 10:30 a.m. – 12:00 p.m. ET, highlighting the progress of its proprietary RP-6306 program for tumors with genetic alterations characterized by CCNE1 amplification (Press release, Repare Therapeutics, APR 8, 2021, View Source [SID1234577736]). The Company expects to initiate a Phase 1 clinical trial of RP-6306 in the second quarter of 2021.

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"At today’s event, we will be reviewing the compelling pre-clinical anti-tumor activity of RP-6306, our first- in-class, selective, oral inhibitor of PKMYT1 to treat CCNE1-amplified, FBXW7-altered and other undisclosed PKMYT1 inhibitor-sensitive cancers. Our in vivo and other pre-clinical data indicate that RP-6306 can selectively inhibit tumors with these specific alterations when used as a monotherapy and in combination with other agents. We plan to initiate a Phase 1 clinical trial during this quarter, which is a quarter ahead of previously announced guidance," said Lloyd M. Segal, President and Chief Executive Officer of Repare. "We look forward to advancing our RP-6306 program into the clinic."

"There is a high unmet medical need for better treatments for patients with homologous recombinant-proficient cancers. The incidence of such cancers is rising and represents a growing therapeutic challenge." said Maria Koehler, MD, PhD, Chief Medical Officer of Repare. "Targeting DNA damage repair using synthetic lethal strategies is a massive opportunity to build on the success of PARP inhibitors. The field is rapidly expanding beyond PARP inhibitors and has been accelerated by the discovery of novel targets enabled by cancer genome sequencing and CRISPR technologies."

Highlights from the Virtual Investor Day

Pre-Clinical Data Findings

Using its proprietary, CRISPR-based SNIPRx discovery platform, Repare has identified PKMYT1 as a strong hit in a CCNE1-overexpression synthetic lethal screen. PKMYT1 is a kinase that phosphorylates CDK1, thereby holding the cyclin B-CDK1 complex in an inactive state until the cell is ready to enter mitosis. The Company’s product candidate RP-6306 is being developed as a highly potent and selective PKMYT1 inhibitor that preferentially kills tumor cells overexpressing CCNE1 and has shown to inhibit the growth of a broad range of CCNE1-amplified tumors in xenograft/PDX preclinical models, both as a single agent and in combination therapy settings. RP-6306 has been observed to have a favorable pre-clinical PK profile as well as low potential for drug-drug interactions. Application of Repare’s STEP2 genome-wide chemical screen has identified other gene alterations beyond CCNE1 amplification that are uniquely targetable by RP-6306, including tumors that have loss of FBXW7 function, a cell-cycle regulator that has been implicated as a key genetic driver in a broad range of cancers, and represent further areas of unmet medical need.

RP-6306 Phase 1 Clinical Trial Design

Repare plans to initiate enrollment of a Phase 1 clinical trial of RP-6306 during this quarter. Study objectives include assessment of safety, tolerability, dose and schedule (including the recommended Phase 2 dose). Subject to completion and review of the Phase 1 clinical trial, the Company expects to advance RP-6306, both as monotherapy and in combination with chemotherapies and other agents, into proof-of-concept studies in 2022 targeting a variety of patient populations, including those with tumors with CCNE1 amplification, FBXW7 loss or other undisclosed alterations identified through its proprietary STEP2 screen. Prospective enrichment of study patient populations will be guided by its ongoing efforts to develop patient selection biomarkers covering both target engagement and functional (DNA damage) readouts.

Virtual Investor Day Agenda

10:30 a.m. – 10:35 a.m. ET

Introduction

Lloyd Segal, President and Chief Executive Officer, Repare Therapeutics

10:35 a.m. – 10:50 a.m. ET

Targeting DNA Damage Repair in the Clinic

Timothy Yap, MBBS, Ph.D., FRCP

Medical Director, Institute for Applied Cancer Science, and Associate Professor, Department of Investigational Cancer Therapeutics, Division of Cancer Medicine at MD Anderson Cancer Center

10:50 a.m. – 11:05 a.m. ET

Genomic Classifications of Endometrial & Ovarian Cancers is Standard of Care

Unmet Need: Therapies Targeting CCNE1 & FBXW7

Carol Aghajanian, M.D.

Chief of Gynecologic Medical Oncology Service and Professor of Medicine, Weill Cornell Medical College, Memorial Sloan Kettering Cancer Center

11:05 a.m. – 11:35 a.m. ET

Target Discovery & Biology of RP-6306 & STEP Characterization Table

Michael Zinda, Ph.D., Executive Vice President, Chief Scientific Officer, Repare Therapeutics

11:35 a.m. – 11:45 a.m. ET

Translational & Clinical Plan for RP-6306

Maria Koehler, M.D., Ph.D., Executive Vice President, Chief Medical Officer, Repare Therapeutics

11:45 a.m. – 12:00 p.m. ET

Conclusion & Q&A Session

Conference Call and Webcast

To access the event virtual event, please dial (833) 638-9655 (U.S. and Canada) or (602) 585-9856 (international) at least 10 minutes prior to the start time and refer to conference ID 1093819. A live video webcast will be available in the Investor section of the Company’s website at View Source A webcast replay will also be available on the corporate website at the conclusion of the call.

About RP-6306

RP-6306, the result of Repare’s proprietary drug discovery program, is a first-in-class, selective, oral inhibitor of PKMYT1 to treat CCNE1-amplified, FBXW7-altered and other PKMYT1 inhibitor-sensitive cancers that typically do not respond well to platinum or PARP inhibitor treatment. Through Repare’s SNIPRx screen campaign for targets that are SL with CCNE1 amplification, the Company identified and validated this novel SL gene that has the characteristics of a therapeutic target. Subsequently, the Company developed novel and selective inhibitors against PKMYT1, which repeatedly demonstrated compelling anti-tumor activity, and announced the advancement of a clinical candidate for this first-in-class program. Repare anticipates initiating a Phase 1 clinical trial of RP-6306 during the quarter ending June 30, 2021. This trial is expected to enroll patients suffering from recurrent tumors characterized by CCNE1 amplification or other genomic alterations predicted to be sensitive to RP-6306. The primary objective of the trial is to assess preliminary safety in patients and to establish the RP2D and schedule for RP-6306 for further studies as a monotherapy. Dependent on Phase 1 result, an additional trial is planned to evaluate the combination of RP-6306 with approved anti-cancer agents, including chemotherapy.

On April 8, 2021 Onxeo S.A. (Euronext Growth Paris: ALONX, First North Copenhagen: ONXEO), ("Onxeo" or "the Company"), a clinical-stage biotechnology company specializing in the development of innovative drugs targeting tumor DNA Damage response (DDR), reported the presentation of preclinical data confirming the differentiated antitumoral properties of the drug candidates generated by platON, its patent-protected platform of decoy-agonists of the DNA Damage Response, in e-poster sessions during the American Association for Cancer Research (AACR) (Free AACR Whitepaper) (AACR 2021) virtual annual meeting on April 10, 2021 (Press release, Onxeo, APR 8, 2021, View Source [SID1234577735]).

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The first e-poster supports the ability of AsiDNA, the Company’s first-in-class DNA Damage Response (DDR) inhibitor, to prevent resistance to KRAS inhibitors (KRASi) emerging from drug-tolerant persister cells (DTC). Novel therapies targeting the inhibition of KRAS, an oncogenic protein present in a third of cancers, have shown very promising clinical results especially in non-small cell lung cancer. However, acquired resistance hinders their efficacy. Combining AsiDNA to KRASi could be an additional development opportunity for AsiDNA, in the context of its use to prevent acquired resistance to targeted therapies.

The second e-poster describes the mechanism of action of the molecules of the new OX400 family, specifically designed to interfere with PARP signaling and display immunomodulatory properties and metabolic effects.

Judith Greciet, Chief Executive Officer of Onxeo, commented: "Pharmaco-tolerant cells are a well-established cause of resistance to TKIs, and, as we already demonstrated last year, to PARP inhibitors. We have generated new data demonstrating that these cells are also involved in resistance to KRAS inhibitors and confirmed the efficacy of AsiDNA on these cells thus preventing or even reversing tumor regrowth. These results open the door for another potential combination with these innovative compounds which show high efficiency but struggle with resistance issues. In parallel, we continue to optimize the efficacy profile of the next candidates from the OX400 family, while keeping the established benefits shared by all our platON-sourced compounds in terms of safety and absence of resistance. Our new results confirm that, by trapping and exhausting specifically PARP, OX400 compounds have the potential to modulate the immune response and wear out the tumor cell metabolism. We will continue to explore these original properties."

Session: PO.ET03.05 – Reversal of Drug Resistance E-poster: 1433

Date/ Time: April 10, 2021 – 8:30 AM – 11:59 PM (U.S. Eastern Daylight Time -EDT)

To read the abstract: Acquired resistance to KRASG12C inhibitors evolves from drug-tolerant persister cells vulnerable to AsiDNA.

Recent progress has been made in the development of therapeutics against KRASG12C mutated tumors, which represent approximately 15% of lung adenocarcinoma. However, therapeutic resistance to KRASG12C inhibition is still a clinical hurdle. As we have previously shown with PARP inhibitors, we describe in these new data that resistance to KRASG12C inhibitors could also emerge, at least in part, from drug-tolerant persister cells, a specific cell population that undergo "dormancy" during treatment and accumulate mutations enabling the development of resistance to KRASG12C inhibitors. AsiDNA can target specifically this source of resistance and therefore prevents the emergence of acquired resistance to KRASG12C inhibitors, pointing to the therapeutic opportunity of combining AsiDNA and KRASG12C to overcome tumor progression or relapse.

Session: PO.CL06.07 – Immunomodulatory Agents and Interventions E-poster: 527

Date/ Time: April 10, 2021 – 8:30 AM – 11:59 PM (U.S. Eastern Daylight Time -EDT)

To read the abstract: A new generation of PARP interfering drug candidates for cancer treatment.

Onxeo pioneered a new approach of anti-cancer treatment to tackle acquired drug resistance: the decoy agonist mechanism of action. Drugs based on this mechanism hijack and hyperactivate therapeutic targets leading to an impairment of their physiological function. Our first compound using this breakthrough decoy agonist action, AsiDNA, has already shown target engagement, excellent safety profile in humans and importantly, lack of acquired resistance. We now describe the mechanism of action of our OX400 molecules, designed to trap PARP proteins. We show that these molecules, by interfering with PARP signaling, display immunomodulatory properties and metabolic effects. Our results provide a preclinical rationale for using OX400 molecules as immunomodulatory and "metabolic exhauster" agents, especially in appropriately molecularly selected patients with tumors showing metabolic deficiencies.

On April 8, 2021 Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC) reported that Dr. Matt Coffey, the Company’s President and Chief Executive Officer, will be participating in a panel discussion at the Canaccord Genuity Horizons in Oncology Virtual Conference (Press release, Oncolytics Biotech, APR 8, 2021, View Source [SID1234577734]). Details on the panel discussion are provided below.

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Title: Off-the-Shelf CAR T – solid tumors, myeloma, lymphoma
Date: Thursday, April 15, 2021
Time: 8:15 am ET

Company management will also be participating in one-on-one investor meetings at the conference. To schedule a meeting, please contact your Canaccord representative or email [email protected].

On April 8, 2021 Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX) reported that Jeffrey L. Wade, Lexicon’s executive vice president, corporate and administrative affairs and chief financial officer, will participate in a live fireside chat at the 20th Annual Needham Virtual Healthcare Conference on Thursday, April 15, 2021 at 10:15 a.m. ET (Press release, Lexicon Pharmaceuticals, APR 8, 2021, View Source [SID1234577732]).

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A webcast of the event will be available in the "Events" section of the Lexicon website at www.lexpharma.com. An archived version of the webcast will be available on the website for two weeks.

On April 8, 2021 IMMUNOPRECISE ANTIBODIES LTD. (the "Company" or "IPA") (NASDAQ: IPA) (TSX VENTURE: IPA) a leader in full-service, therapeutic antibody discovery and development, reported that its subsidiary Talem Therapeutics LLC ("Talem") has advanced development of a candidate panel of vetted, novel, therapeutic antibodies, collectively referred to as TATX-112, against an undisclosed target, into formal lead candidate characterization (Press release, ImmunoPrecise Antibodies, APR 8, 2021, View Source [SID1234577731]).

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It is well documented that certain genes, when mutated and expressed in different tissues and organs, may play a role in more than one disease.

Oncology

The target is a protein receptor that is overexpressed in a variety of types of deadly cancers. In solid tumors, stimulation of the target by its ligand is described to result in activation of intracellular signaling pathways that promote cancer cell growth, survival, invasiveness, metastatic behavior, and suppress chemotherapeutic sensitivity of the tumor cells. Therefore, interference with the target signaling is anticipated to be an attractive approach to induce tumor suppression, or halting tumor cell growth. As current therapies focusing on inhibiting intracellular target signaling consist primarily of non-target selective small molecule inhibitors, they may be high risk for unintentionally causing undesirable side-effects to the patient by functionally blocking related receptor proteins, which are more widely expressed in the human body, in parallel. In contrast, Talem has developed the TATX-112 antibodies with the goal of specifically blocking the interaction between the target and its ligand, e.g. functionally interfering with the target’s biology, which is expected to significantly improve specificity of such tumor therapy due to its relatively higher expression levels in tumors compared to normal tissue. That higher specificity is expected to increase the therapeutic window by lowering the potential risk of side effects and positively impacting treatment efficacy. Additionally, the target’s expression profile makes this membrane protein a promising candidate for antibody-drug conjugate-based therapies.

Neurodegenerative Diseases

In addition to its role in oncology, the target plays a vital role in the nervous system by enhancing neuronal development, survival, protection, and function. Alzheimer’s and other neurodegenerative diseases are associated with reduced expression levels of the target and impaired receptor signaling. Stimulating intracellular target signaling using agonistic antibodies is an appealing therapeutic approach to suppress disease progression with an expectedly higher safety profile than less-selective small molecules. Such therapeutic strategy requires blood-brain-barrier passage which can be facilitated by a bi- or multi-specific antibody format, including an antibody fragment that induces transport over the blood-brain-barrier upon binding.

Talem’s Pipeline

As the different clinical application options for TATX-112 antibodies require a functionally diversified set of lead candidates and antibody format flexibility, Talem relied on two of IPA’s proprietary target-enrichment antibody discovery platforms, B cell Select and DeepDisplay. Following selection of both target-reactive B cells from target immunized chicken and human scFvs from IPA’s in-house phage libraries, 50 sequence-unique antibodies of particular interest were prioritized for more in-depth characterization to bin antibodies for further (indication-specific) clinical development.

In addition to TATX-112, Talem is continuing development efforts of its other potential products leveraging its pipeline of highly differentiated therapeutic antibody programs for the potential treatment of various disease areas, including heart disease, inflammation, infectious diseases and cancer. The Company’s most advanced development program, TATX-03 ("anti-SARS PolyTope"), is a fully human, synergistic, antibody cocktail containing potently neutralizing antibodies against non-overlapping epitopes on SARS-CoV-2.

"Generating a diversified anti-target antibody panel during the discovery phase is key to a successful therapeutic lead campaign, in particular for programs that are aimed at obtaining antibodies with different modes of action," stated ImmunoPrecise President and CEO, Dr. Jennifer Bath. Leveraging our robust target-enrichment antibody discovery technologies, B cell Select and DeepDisplay, we discovered a highly sequence diverse pool of anti-target antibodies, which allows proper down-selection of the best-performing lead candidates for further development, thereby increasing the chance of successful clinical application."

About B cell Select

IPA’s B cell Select platform enables the interrogation of a greater diversity of an antibody repertoire. By interrogating isolated B cells, IPA can analyze full organism repertoires with very little manipulation. This proprietary platform is species independent allowing for the generation of antibodies from samples not possible using other methods. B cell Select has the potential to develop antibodies from any species (including humans) as well as from any tissue. As the platform explores the entire antibody repertoire, it provides the opportunity to develop antibodies for anything that is possible in an animal’s immune repertoire including any protein class, complex therapeutic targets, post-translational modifications, and small molecules.

The B cell Select platform enables the interrogation of 10 million blood cells to generate native monoclonal antibodies from immunized animals that specifically target an antigen. The B cell Select process takes place early in the antibody development process allowing for the rapid selection of top candidates, drastically increasing the success rate of antibody discovery. The platform also harnesses the power of the immune system to generate natural pairing of the antibodies produced by selected B cells.

About DeepDisplay

IPA’s DeepDisplay is a phage display approach based on building custom immune libraries from multiple species, including transgenic animals, or the selection of antigen-specific recombinant antibody fragments from our proprietary human or llama phage libraries. Our libraries have been made from human patient and naïve (scFv) repertoires, as well as from naïve llama (VHH) repertoires. Custom immune libraries are prepared from blood, spleen, lymph nodes, and bone marrow of immunized animals or humans and capture the entire immune repertoire for panning, rescue, and identification of unique antibodies with pre-specified characteristics.