1stOncology™: Cancer Intelligence Service – Page 10138 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

Poseida shares plunge after death in solid tumor CAR-T trial, clinical hold

On August 18, 2020 Poseida Therapeutics reported its shares plummet after-hours Monday when it revealed in a Securities and Exchange Commission (SEC) filing that its cancer drug has been slapped with a full clinical hold (Press release, Poseida Therapeutics, AUG 18, 2020, View Source [SID1234563884]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

Schedule Your 30 min Free Demo!

The hold has hit its phase 1 test for P-PSMA-101 in metastatic castration-resistant prostate cancer and comes after a patient died of liver failure in the study, the cause of which could "possibly related to P-PSMA-101 pending further investigation," the biotech said in the SEC filing.

"Although the direct cause of the hepatic failure has not yet been confirmed, the patient developed symptoms consistent with macrophage activation syndrome (MAS)," Poseida explained. "MAS is a serious and potentially fatal overactivation of the immune system which has been associated with CAR-T therapies, but can have other causes such as infection and autoimmune disease.

WHITEPAPER
Humanized Mouse Models for Drug Discovery: The NOG Portfolio
Human immune system mouse models are leading to breakthroughs in a wide range of research applications. In this white paper, explore the NOG portfolio and the unique benefits of each model to determine the appropriate choice for your study.
GET YOUR COPY NOW!
"The patient also developed blurred vision which was diagnosed as uveitis. The clinical investigator has assessed the SAE as possibly related to P-PSMA-101 pending further investigation." The patient died 17 days after receiving the therapy.

Shares in the biotech, which has been strongly backed by Novartis in its early funding rounds, fell 34% on the news.

It is now awaiting a formal response from the FDA and is "preparing recommendations designed to allow resumption of the clinical trial."

The drug is its first solid tumor autologous CAR-T product candidate targeting prostate-specific membrane antigen, or PSMA. The most success with CAR-T has been across blood cancers, but, like a growing number of other biotechs, Poseida was hoping to unlock its potential in solid tumors.

Poseida had IPO’d this summer on the strength of its pipeline, which includes P-PSMA-101 and leading drug P-BCMA-101, an autologous CAR-T currently in a potentially registrational phase 2 trial for multiple myeloma.

Toxicity in cell therapy has long been an issue for this new cancer R&D area, and Poseida is not the first biotech to be hit by CAR-T trial deaths, with Juno Therapeutics (bought by Celgene, which was bought by Bristol Myers Squibb), seeing a group of deaths in mainly young people from its now ditched CAR-T JCAR015. Here, the deaths were caused by cerebral edema.

Poseida only got off its IPO last month, worth $224 million and valuing the biotech at a cool $1 billion. That second IPO attempt came a year after ditching its first in favor of a new funding round led by Novartis, which was worth a major $142 million.

And, in the middle of its second IPO attempt, it found time to raise a quick $110 million in private funding.

Merck to Build $1.3 Billion Research Hub in London

On August 18, 2020 Merck, known as MSD in Europe to distinguish it from Germany’s Merck KGaA, Darmstadt, Germany, reported that moving ahead with its $1.3 billion research center in London (Press release, Merck & Co, AUG 18, 2020, View Source [SID1234563826]). The plan was originally announced in 2017 as part of a pledge to support post-Brexit Britain. The project has been delayed a bit, some of that related to difficulties in finding space in London, and also because it wanted to be in the life sciences hub near the Francis Crick Institute in north London. Merck has a significant five-year neuroscience research-and-development deal with the Crick Institute.

The new research hub will be called the London Discovery Research Centre and is expected to open by 2025. Work is expected to begin late next year, and the site expects to create approximately 120 new jobs for researchers and technicians and employ about 800 people overall. The site is expected to be 25,000 square meters.

"We currently view the UK as a world leader in developing science, driven by the long-term emphasis on building a strong research and development infrastructure," David Peacock, MSD managing director for UK and Ireland, told the Financial Times.

The new site is across from King’s Cross station. The deal has not been finalized yet, requiring the council for the London borough of Camden to sign off on it. And there are reports of at least one group that is protesting the move.

A group of brick buildings called Belgrove House are currently at the site and would need to be demolished for the research center to go in. A local activist who is anonymous but runs SaveBloomsbury.co.uk has called the plan "diabolical" and described the plans for the center’s structure a "monstrosity" inappropriate for the neighborhood.

The protester wrote, "Despite being situated in one of the most highly sensitive historic settings in London, the development is one of the ugliest and most inappropriate buildings proposed in recent times, rivaling the Town Hall Annexe itself for the title of ugliest building in Camden."

If Camden’s council approves, Merck will begin construction late in 2021 and finish by 2025, which is five years after the date originally proposed. According to the Financial Times, the researchers at the site will run early-stage research and mostly focus on age-related diseases.

As the 2018 story out of the Crick Institute noted, a team of about 15 Merck chemists and pharmacologists have been based there while plans to build the site have dragged on. The Merck team’s research projects were independent from Crick research, but the team was fully integrated into the Crick scientific community.

In August 2019, researchers from Merck and Crick began a new collaboration to focus on the causes of Motore Neurone Disease. It was the first project out of the five-year collaboration. Motore Neurone Disease is better known as Amyotrophic Lateral Sclerosis (ALS). The project is led by Rickie Patani, a research group leader at Crick and UCL and a consultant neurologist at the National Hospital for Neurology and Neurosurgery.

At the time, Rickie said, "In the clinic, it’s devastating when I have to tell a patient they have Motor Neurone Disease. Often, the patient first walks in with mild weakness in a limb and then I see the disease progressing relentlessly with every visit. Within a year or two, they might be in a wheelchair and require breathing support. This disease destroys families, and I feel profoundly guilty that we still have no effective treatments to offer."

He added, "Through fundamental research, we want to understand the basic biology underpinning the disease. Just knowing what’s happening can offer some comfort to patients, even when there aren’t treatments around the corner."

AIkido Pharma Sponsors Survival Study of University of Kentucky Anticancer Drug G4-1 in Exchange for Exclusive Option to License

On August 18, 2020 AIkido Pharma Inc. (Nasdaq: AIKI) ("AIkido" or the "Company") reported that it will provide funding for a 30-day survival study in mice in collaboration with University of Kentucky related to the anticancer drug designated G4-1, a novel proteasome inhibitor (Press release, AIkido Pharma, AUG 18, 2020, View Source [SID1234563806]). In exchange, Aikido has been granted an exclusive option to license the drug ("Option") pending the results of the study.

The Option includes two issued patents, United States Patent Nos. 9,493,439 and 9,586,946, each having expiration dates in the mid-2030’s. AIkido was previously granted an option to license these patents, which it did not exercise in favor of performing this further research.

Mr. Anthony Hayes, CEO of AIkido stated, "The published mouse data on G4-1 shows exciting promise for the treatment of solid tumors compared to already approved drugs. Given those encouraging preliminary results, we agreed to fund a survival study to determine whether G4-1 can also increase survival over the marketed drugs. This transaction represents another low-risk initiative to bolster our portfolio. We optimistically anticipate the results of this study and hope they support adding G4-1 to our oncology products."

Dr. Chang-Guo Zhan, Professor, College of Pharmacy at the University of Kentucky, added, "Proteasome inhibitors in current clinical use are all peptides with very low in vivo stability. G4–1 is a non-peptide proteasome inhibitor with the desirably high in vivo stability required for the treatment of solid tumors. We are excited about the opportunity to further evaluate the therapeutic potential of G4-1 with funding supporting from AIkido."

CARMA Cell Therapies™ Expands Phase I Trial of Anti-Mesothelin mRNA CAR-PBMC Cell Therapy MCY-M11

On August 18, 2020 MaxCyte, Inc., a global cell-based therapies and life sciences company, reported the expansion of subsidiary CARMA Cell Therapies’ ongoing Phase I intraperitoneal delivery and dose-escalation trial of MCY-M11, its lead anti-mesothelin CAR-PBMC cell therapy candidate (Press release, MaxCyte, AUG 18, 2020, View Source [SID1234563802]). The expansion will involve a new parallel cohort of patients and the initiation of two additional clinical sites.

The new parallel Phase I cohort will evaluate intraperitoneal delivery of MCY-M11 at escalating doses in additional patients with relapsed/refractory ovarian cancer and malignant peritoneal mesothelioma, with the addition of a preconditioning regimen of cyclophosphamide prior to MCY-M11 infusion. This parallel Phase I cohort with preconditioning will progress independently from the ongoing evaluation of MCY-M11 in the existing no-preconditioning Phase I cohort. The MCY-M11 Phase I trial will also allow for multiple treatment cycles where indicated for both future preconditioning and no-preconditioning patients.

New clinical sites for the study at Massachusetts General Hospital/Harvard Medical School and Hackensack University Medical Center are joining existing sites at the National Cancer Institute at the National Institutes of Health and Washington University in St. Louis.

In May, encouraging preliminary results for MCY-M11, which support this study expansion and the pursuit of new strategies with the therapy, such as the addition of a preconditioning regimen and delivering multiple cycles of treatment to further enhance efficacy, were presented at the virtual ASCO (Free ASCO Whitepaper) meeting. Results to date also support the continued validation of MaxCyte’s proprietary CARMA autologous cell therapy platform.

For the ASCO (Free ASCO Whitepaper) abstract, please visit: View Source

Following the expansion of the Phase I trial, preliminary clinical data for the existing no-preconditioning MCY-M11 trial are anticipated in H2 2020.

"We are very pleased with the progress of this first-in-human trial to date, and have great hopes that we are moving closer towards bringing a more effective immunotherapeutic option for patients with solid tumors," said Claudio Dansky Ullmann, MD, Chief Medical Officer of MaxCyte.

About MCY-M11

MCY-M11 is a non-viral, mRNA-based anti-mesothelin CAR-PBMC cell therapy manufactured using un-manipulated peripheral blood mononuclear cells (PBMC). It is being evaluated in the clinic as treatment for high mesothelin expressing solid tumors. It is under ongoing development in a first-in human multi-center, non-randomized, open label, dose-escalation Phase I clinical trial evaluating the safety and preliminary efficacy of intraperitoneal infusions of MCY-M11 in individuals with platinum-resistant, high-grade, serous adenocarcinoma of the ovary, primary peritoneum or fallopian tube, or individuals with advanced peritoneal mesothelioma, with recurrence after prior chemotherapy. MaxCyte anticipates 27 study participants will be enrolled across the existing and the new parallel cohort. Interim results presented at the ASCO (Free ASCO Whitepaper) 2020 meeting show that intraperitoneal infusion of MCY-M11 is feasible, safe, and well tolerated. There have been no dose-limiting toxicities and no treatment related discontinuations or deaths and most reported treatment related adverse events have been Grades 1-2 per NCI CTCAE in three completed dose levels as a single agent in the existing cohort. Enrollment in the fourth dose level of the existing cohort is in progress and will run alongside with enrollment in the new parallel cohort that includes a preconditioning regimen. Multiple cycles of treatment will be allowed in both the fourth dose level of the existing cohort and at all dose levels in the new parallel preconditioning cohort. We currently anticipate preliminary clinical data in H2 2020. More information about the study can be found at ClinicalTrials.gov (Identifier: NCT03608618).

ImmPACT Bio USA Inc. Raises $18 Million In Series A Financing

On August 18, 2020 ImmPACT Bio USA Inc., a company founded in the FutuRx incubator located in Ness Ziona, Israel, developing novel cell therapies for treating cancer, reported the closing of a US$ 18 million equity financing round (Press release, ImmPACT-Bio, AUG 18, 2020, View Source [SID1234563800]). The financing included OrbiMed, Johnson & Johnson Innovation – JJDC, Inc., Takeda Ventures, Inc., RM Global Partners (RMGP) BioPharma Investment Fund, Novartis Venture Fund, Bukwang Pharmaceutical, Hayan Health Networks, Inc., and JVC Investment Partners.

ImmPACT Bio USA Inc. is developing a novel set of engineered T-cell therapeutics that target loss of genes in solid tumors. The company was founded based on the insights of Prof. Gideon Gross (Migal Research Institute), who collaborated with Prof. Zelig Eshhar to design the first Chimeric Antigen Receptor technologies for T-cells (CAR T). While CAR-T drugs have provided meaningful breakthroughs for the treatment of some hematologic malignancies, little progress has been made in applying the technology to solid tumors. Such diseases are rarely characterized by the over-expression of tumor-selective antigens, but genomic analyses have revealed many mechanisms for loss of expression.

Founder Prof. Gideon Gross explains ImmPACT’s origins by observing, "Engineered cells have progressed tremendously in lymphomas and leukemias, in large part because lymphocytes have very selective targets. We will need new targeting strategies to tackle solid tumors, as few selective targets have been discovered, and antigens are almost always shared by indispensable tissues." Prof. Gross ultimately realized that, "Many solid tumors demonstrate genetic losses due to abnormal chromosomal maintenance – a fact that can be utilized to design new types of cellular immuno-oncology drugs."

"We have built a world-class team and a promising pipeline to realize Prof. Gross’ vision of targeting loss-of-gene features of solid tumors. We look forward to working with our investors to advance this pipeline and make the company a success," said Rick Kendall, Ph.D., CEO of ImmPACT Bio USA Inc.