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."

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.

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.

Horizon Pharma plc to Release First-Quarter 2019 Financial Resultsand Host Webcast on May 8, 2019

On April 9, 2019 Horizon Pharma plc (Nasdaq: HZNP) reported that its first-quarter 2019 financial results will be released on Wednesday, May 8, 2019. Following the announcement, Horizon’s management will host a live webcast at 8 a.m. Eastern Time to review the Company’s financial and operating results (Press release, Horizon Pharma, APR 9, 2019, View Source [SID1234535313]).

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The live webcast and replay may be accessed at View Source Please connect to the Company’s website at least 15 minutes before the live webcast to ensure adequate time for any software download that may be needed to access the webcast.

Forbius Chief Scientific Officer, Dr. Maureen O’Connor-McCourt, to Present at PEGS Boston’s 9th Annual Clinical Progress of Antibody-Drug Conjugates

On April 9, 2019 Forbius, a clinical-stage company that develops novel biologics for the treatment of cancer and fibrosis, reported that Dr. Maureen O’Connor-McCourt, Chief Scientific Officer of Forbius, will be presenting an overview of AVID100, a novel, tumor-selective, anti-EGFR antibody-drug conjugate (ADC), at PEGS Boston’s 9th Annual Clinical Progress of Antibody-Drug Conjugates (Press release, Forbius, APR 9, 2019, View Source [SID1234535091]).

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Details and highlights of Dr. O’Connor-McCourt’s presentation:

Discovery of Next-Generation ADCs: Preclinical and Clinical Development of AVID100, an EGFR-Targeting ADC

Presentation Friday, April 12th at 11:35 AM ET, Harborview 1 & 2

AVID100 is highly potent and selectively cytotoxic against EGFR-expressing cancer cells, while sparing normal EGFR-positive keratinocytes
AVID100 was well-tolerated in a Phase 1 dose-escalation study in patients with advanced solid tumors of epithelial origin (any EGFR status)
Only modest skin toxicity observed, in line with preclinical findings
Phase 2 trial (AVID100-01; NCT03094169) ongoing to evaluate AVID100 efficacy, safety, and tolerability in patients with EGFR-overexpressing (IHC 3+) SCCHN and sqNSCLC
About AVID100 and the AVID100-01 Trial
AVID100 is a highly potent EGFR-targeting antibody-drug conjugate (ADC) that was engineered to achieve enhanced anti-tumor efficacy without a corresponding increase in toxicity against skin and other EGFR-expressing normal tissues. In preclinical studies, AVID100 demonstrated significant anti-cancer activity, including in EGFR-overexpressing tumor models that are resistant to marketed EGFR inhibitors. AVID100 is the only anti-EGFR ADC in clinical development that targets both wild-type and mutant forms of EGFR.

In a successfully completed Phase 1 study, AVID100 reported a recommended Phase 2 dose (RP2D) of 220 mg/m2 (~6mg/kg), which is expected to be in the therapeutically active range based on preclinical efficacy studies. Treatment was generally well-tolerated, with the majority of treatment-related adverse events in the Phase 1 trial at the RP2D being grade 1 or 2 in severity.

AVID100-01 (NCT03094169) is an open label, multicenter study to evaluate the efficacy, safety, and tolerability of AVID100 in patients with confirmed EGFR-overexpressing tumors (more than 50% of cells with EGFR 3+ or more than 75% of cells with EGFR 2+ staining by a validated immunohistochemistry assay).