Immatics Initiates Third Phase I Clinical Trial of its Unique ACTengine® Platform in Patients with Advanced Solid Cancers

On April 9, 2019 Immatics, a leading company in the field of cancer immunotherapy, reported that it has initiated enrollment of patients into a phase I trial of IMA203, its third T-cell receptor (TCR)-transduced adoptive cell therapy program (Press release, Immatics Biotechnologies, APR 9, 2019, View Source [SID1234569546]). IMA203 is an investigational immunotherapy which uses Immatics’ proprietary ACTengine approach and is based on genetic engineering of the patient’s own T cells to express an exogenous TCR. The goal is to redirect and activate the T cells to treat solid tumors.

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The clinical study (IMA203-101) is now open for enrollment at The University of Texas MD Anderson Cancer Center in Houston, Texas. It will initially include approximately 15 patients with relapsed and/or refractory solid tumors, for which no standard of care therapy is available.

Immatics’ ACTengine approach engineers the patient’s own T lymphocytes (a type of white blood cell) to express a novel, exogenous T-cell receptor (TCR) which is targeted to a site on the tumor identified by Immatics’ proprietary XPRESIDENT target discovery platform. ACTengine combines several innovative features:

Patients are eligible for ACTengine cell therapy if the target of interest is present on the patient’s tumor as demonstrated by biomarker profiling.
The TCR used in this trial has been selected from the human T-cell repertoire of more than one hundred TCRs for highest specificity, using Immatics’ XPRESIDENT-guided on- and off-target toxicity screening.
The novel TCR recognizes its target with optimal affinity to enable an adoptive cellular therapy (ACT) approach that uses a proprietary TCR chain pairing enhancement technology for IMA203 to maximize the efficacy and safety features of ACTengine.
The TCR-transduced T cells are activated and multiplied outside of the body before being infused into the patient. For IMA203, this process requires only 5-6 days of manufacturing time, allowing patients to be treated earlier than with most other comparable therapies.
The primary objective of the study is to evaluate the safety and tolerability of the ACTengine approach, and specifically IMA203, in target-positive solid cancer patients.
The secondary objectives include the evaluation of feasibility, the persistence of T cells in vivo, and the assessment of anti-tumor activity and biomarkers.
The IMA203 phase I trial will be conducted by the Department of Investigational Cancer Therapeutics and the Department of Gynecologic Oncology and Reproductive Medicine at MD Anderson Cancer Center in Houston, Texas. The principal investigators are Dr. Apostolia Tsimberidou and Dr. Amir Jazaeri.
Stephen L. Eck, M.D., Ph.D., Chief Medical Officer of Immatics US, commented: "This new study will be the third in Immatics’ series of ACTengine studies which modify a patient’s existing T cells to recognize highly specific tumor antigens. These studies were built from Immatics’ unique XPRESIDENT target discovery technology, which identifies novel tumor-specific T-cell targets. IMA203 will focus on a patient population distinct from that of our other studies, expanding the tumor indications Immatics seeks to treat. Collectively, the ACTengine series of studies address a broad spectrum of human cancers by providing a therapy for each patient that is based on each individual’s unique tumor biology."

Bio-Techne To Host Conference Call On April 30, 2019 To Announce Third Quarter 2019 Financial Results

On April 9, 2019 Bio-Techne Corporation (NASDAQ:TECH) reported that management will host a conference call on Tuesday, April 30, 2019 at 8:00 a.m. CDT to review third quarter 2019 financial results (Press release, Bio-Techne, APR 9, 2019, https://investors.bio-techne.com/news/detail/133/bio-techne-to-host-conference-call-on-april-30-2019-to-announce-third-quarter-2019-financial-results [SID1234536923]).

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Access to the discussion may be obtained as follows:

Time:

8:00 a.m. CDT

Date:

April 30, 2019

Dial-in:

1-866-548-4713 or 1-323-794-2093 (for international callers)

Conference ID:

9482573

A recorded rebroadcast will be available for interested parties unable to participate in the live conference call. To access the recording, U.S. callers should dial 1-844-512-2921 or international callers should dial 1-412-317-6671 and enter the replay access code 9482573. The recording can also be accessed by going to:

View Source

The replay will be available from 11:00 a.m. CDT on Tuesday, April 30, 2019 until 11:00 p.m. CDT on Thursday, May 30, 2019.

Case Report in the Journal of Neurosurgery Highlights Potential of ONC201 in H3 K27M-mutant DIPG

On April 9, 2019 Oncoceutics reported the publication of an article entitled "First clinical experience with DRD2/3 antagonist ONC201 in H3 K27M–mutant pediatric diffuse intrinsic pontine glioma: a case report" in the Journal of Neurosurgery (authored by Matthew D. Hall, M.D., MBA) (Press release, Oncoceutics, APR 9, 2019, View Source [SID1234558359]). The article summarizes the medical history of a 10-year-old girl with a diffuse intrinsic pontine glioma (DIPG) brain tumor. Following radiation therapy and treatment with ONC201 on a compassionate use basis, she developed near complete resolution of her presenting neurological symptoms for almost one year, enabling her return to school and participation in many normal activities.

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DIPG is a serious and rare disease with a dismal prognosis and no viable treatment options. It predominantly affects children and young adults, and it is the most common form of brainstem glioma in this age group. DIPG.org, a resource network for the disease, summarizes the disease characteristics as follows: "Currently, outcomes for most patients are poor, with a median survival of less than 1 year from diagnosis. Radiation therapy can shrink tumors, temporarily improving some symptoms and delaying the progression of the disease, but in almost all cases, the tumor continues to grow. So far, clinical trials have not shown that currently available chemotherapy drugs, radiosensitizing drugs (drugs that make tumor cells more likely to be killed by radiation therapy), or biologics (medical products created by biological processes, such as vaccines or gene therapy) benefit patients. Because of their location in the brainstem, DIPGs cannot be removed surgically. New approaches to treating DIPG are urgently needed."

ONC201 is an investigational drug developed by Oncoceutics that is being studied in several clinical trials for use against DIPG and other brain tumors. The underlying mechanism of the drug involves the interception of a specific receptor for dopamine, called DRD2. DRD2 is a neurotransmitter that is misused by malignant glioma cells to boost their growth. Tumors that harbor a certain mutation of a highly conserved histone protein, i.e. H3 K27M, are particularly sensitive to ONC201 in spite of the otherwise aggressive growth that this mutation confers. DIPG is one of the tumor types that exhibit a high prevalence of this mutation.

The patient described in the article has shown prolonged clinical benefits and is approaching almost two years from diagnosis, although ONC201 was administered only when symptoms progressed after radiation was completed. This supports further investigation of ONC201 in H3 K27M-mutant gliomas, including DIPG. As a result, Oncoceutics has significantly expanded its pediatric clinical program for ONC201. The company’s ongoing pediatric trial for ONC201 in H3 K27M-mutant high-grade gliomas including DIPG (NCT03416530) was extended with additional treatment arms, a pediatric oral solution formulation was introduced, and ONC201 treatment was extended to newly diagnosed DIPG patients with concomitant radiation.

The company further implemented an intermediate size Expanded Access Protocol (EAP) to provide access to ONC201 for patients that might benefit from the drug but are not eligible for participation in the ongoing clinical trials. The EAP was made possible by the support of the Food and Drug Administration and their high priority effort to facilitate access to promising medicines for patients with serious or immediately life-threatening diseases or conditions when no comparable or satisfactory alternative therapy options are available (see recent FDA statement). The program is also supported by The Musella Foundation, The Cure Starts Now Foundation, The Michael Mosier Defeat DIPG Foundation, Cancer Commons and xCures.

"We are delighted to see a novel concept to treat this horrible disease emerge and show traction in clinical settings," said Keith Desserich, Chairman of the Board and Co-Founder of The Cure Starts Now. "We have followed the development of ONC201 for some time and are excited about the emerging data in both, children as well as young adults that are expected to become public later in this year.

BerGenBio to Present at H.C. Wainwright Global Life Sciences Conference

On April 9, 2019 BerGenBio ASA (OSE:BGBIO), a clinical-stage biopharmaceutical company focused on developing a pipeline of first-in-class drug candidates targeting AXL kinase to treat aggressive diseases including immune-evasive and therapy resistant cancers, reported that Richard Godfrey, BerGenBio’s Chief Executive Officer, will present an overview of the Company at the H.C. Wainwright Global Life Sciences Conference today, April 9, 2019 (Press release, BerGenBio, APR 9, 2019, View Source [SID1234535054]).

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Date:

Tuesday, April 9, 2019

Time:

09:10 AM BST

Location:

JW Marriott Grosvenor House, London, UK

The presentation slides will be available on www.bergenbio.com in the investor section at time of presentation.

Daiichi Sankyo’s EZH1/2 Dual Inhibitor Valemetostat (DS-3201) Receives SAKIGAKE Designation for Treatment of Patients with Relapsed/Refractory Peripheral T-Cell Lymphoma from Japan MHLW

On April 9, 2019 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) reported that valemetostat (DS-3201), an investigational and potential first-in-class EZH1/2 dual inhibitor, has received SAKIGAKE Designation for the treatment of adult patients with relapsed/refractory peripheral T-cell lymphoma (PTCL) by the Japan Ministry of Health, Labour and Welfare (MHLW) (Press release, Daiichi Sankyo, APR 9, 2019, View Source [SID1234535072]).

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"There is a need for new and novel treatment approaches for patients with peripheral T-cell lymphoma, a group of heterogenous diseases for which relapse rates tend to be high and options beyond systemic chemotherapy are limited," said Kaszushi Araki, Valemetostat Global Team Leader, Oncology Clinical Development Department, Oncology Function, Daiichi Sankyo. "We look forward to working closely with the Japan Ministry of Health, Labour and Welfare to optimize development of valemetostat and to potentially offer a new, first-in-class targeted therapy option for patients with various subtypes of relapsed/refractory PTCL, including those that are more common in Japan."

The SAKIGAKE Designation System promotes R&D in Japan, driving early practical application for innovative pharmaceutical products, medical devices, and regenerative medicines. As a designated medicine under the SAKIGAKE Designation System, valemetostat will have prioritized consultation, a dedicated review system to support the development and review process, as well as reduced review time from the normal 12 months to 6 months.

Valemetostat targets epigenetic regulation by inhibiting both the EZH1 (enhancer of zeste homolog 1) and EZH2 (enhancer of zeste homolog 2) enzymes that act through histone methylation to regulate gene expression.[1] Reactivation of the silenced genes results in decreased proliferation of EZH2-expressing cancer cells.1 Preclinical research has shown that valemetostat suppressed trimethylation of H3K27 in cells more strongly than EZH2 selective inhibitors.[2] Valemetostat also displayed antitumor activity in various hematological malignancies in preclinical models.2,[3]

SAKIGAKE Designation was granted based on the preliminary results of an ongoing phase 1 study assessing the safety and efficacy of valemetostat in patients with non-Hodgkin lymphomas (NHL) including PTCLs, which were presented at the 2017 annual meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper).[4]

About Peripheral T-Cell Lymphoma (PTCL)

Peripheral T-cell lymphoma (PTCL) is a subtype of non-Hodgkin lymphoma (NHL), a form of cancer that originates in lymphocytes, a type of white blood cell.[5] The two main types of NHL are B-cell lymphomas and T-cell lymphomas, which are classified into subtypes based on the origin and stage of the cancer.[6]

There are at least eight different types of PTCL.[7] Each type is considered rare. Global incidence of PTCL subtypes varies by geographic region.[8] Most, but not all, types of PTCL are aggressive, and patients are usually treated with systemic chemotherapy; relapse is common after initial treatment.8

The incidence of lymphoma, including NHL, is increasing year by year around the world.[9] There were an estimated 509,000 new cases and about 248,000 deaths globally from NHL in 2018.[10] In Japan, there were nearly 21,000 new cases of NHL in 2012.[11] While recent treatment advances have led to improved outcomes for patients with certain types of NHL, patients with aggressive NHL subtypes or relapsed/refractory disease still face a poor prognosis.6,[12]

About Valemetostat

Part of the investigational AML Franchise of the Daiichi Sankyo Cancer Enterprise, valemetostat is an investigational and potential first-in-class EZH1/2 dual inhibitor in phase 1 clinical development for hematologic cancers including acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), and Non-Hodgkin lymphoma (NHL), including adult T-cell leukemia/lymphoma (ATL/L), peripheral T-cell lymphoma (PTCL), and B-cell lymphomas. Valemetostat is an investigational agent and has not been approved by the FDA or any other regulatory agency worldwide as a treatment for any indication. Safety and efficacy have not been established.

About Daiichi Sankyo Cancer Enterprise

The mission of Daiichi Sankyo Cancer Enterprise is to leverage our world-class, innovative science and push beyond traditional thinking to create meaningful treatments for patients with cancer. We are dedicated to transforming science into value for patients, and this sense of obligation informs everything we do. Anchored by three pillars including our investigational Antibody Drug Conjugate Franchise, Acute Myeloid Leukemia Franchise and Breakthrough Science Franchise, we aim to deliver seven distinct new molecular entities over eight years during 2018 to 2025. Our powerful research engines include two laboratories for biologic/ immuno-oncology and small molecules in Japan, and Plexxikon Inc., our small molecule structure-guided R&D center in Berkeley, CA. Compounds in pivotal stage development include: DS-8201, an antibody drug conjugate (ADC) for HER2 expressing breast, gastric and other cancers; quizartinib, an oral selective FLT3 inhibitor, for newly-diagnosed and relapsed/refractory acute myeloid leukemia (AML) with FLT3-ITD mutations; and pexidartinib, an oral CSF-1R inhibitor, for tenosynovial giant cell tumor (TGCT). For more information, please visit: www.DSCancerEnterprise.com.