On March 5, 2021 BerGenBio ASA (OSE:BGBIO), a clinical-stage biopharmaceutical company developing novel, selective AXL kinase inhibitors for severe unmet medical need, reported the first patient dosed in an international Phase Ib trial investigating its first-in-class fully humanised anti-AXL monoclonal antibody, tilvestamab (BGB149) (Press release, BerGenBio, MAR 5, 2021, View Source [SID1234578613]).

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The objective of the study is to confirm safety, tolerability and determine a recommended phase II dose (RP2D) for use in subsequent clinical trials. It is a multiple ascending dose study, that will focus on establishing tilvestamab’s
safety profile, tolerability and provide an insight into the dose proportional response with respect to its effectiveness at modulating AXL expression, as determined by BerGenBio’s proprietary cAXL biomarker diagnostic assay.

The study will be conducted in patients with platinum resistant high-grade serous ovarian cancer, in which AXL is frequently strongly over expressed. The research will be conducted at specialist ovarian cancer centres able to perform serial biopsies in these patients, and thereby providing a comprehensive understanding of how tilvestamab modulates AXL expression in real time during a treatment period.

Richard Godfrey, Chief Executive Officer of BerGenBio, said: "We understand that AXL plays an important role in mediating the aggressive nature of this treatment resistant cancer. From our Phase Ia study with tilvestamab that was completed last year, we have an insight into its safety profile, and a safe starting dose for this first-in-patient study. I am particularly excited that we are able to conduct this state-of-the-art study collecting serial biopsies from patients with a similar disease, which will provide high quality data on how tilvestamab modulates AXL expression. This will inform how we can best use tilvestamab in a future Phase II program.

About AXL

AXL kinase is a cell membrane receptor and an essential mediator of the biological mechanisms underlying life-threatening diseases.

In COVID-19, AXL has two synergistic mechanisms of action, it acts a co-receptor to ACE2, to which the spike protein of the Sars-Cov-2 virus attaches and enters the host cell, and AXL expression is upregulated that leads to suppression of the Type 1 Interferon immune response by host cells and in their environment. Research data confirms bemcentinib inhibits SARS-CoV-2 host cell entry and promotes the anti-viral Type I interferon response.

In cancer, increase in AXL expression has been linked to key mechanisms of drug resistance and immune escape by tumour cells, leading to aggressive metastatic cancers. AXL suppresses the body’s immune response to tumours and drives treatment failure across many cancers. High AXL expression defines a very poor prognosis subgroup in most cancers. AXL inhibitors, such as bemcentinib, therefore, have potential high value as monotherapy and as the cornerstone of cancer combination therapy, addressing significant unmet medical needs and multiple high-value market opportunities. Research has also shown that AXL mediates other aggressive diseases including fibrosis.

About Bemcentinib

Bemcentinib (formerly known as BGB324), is a potential first-in-class, potent and highly selective AXL inhibitor, currently in a broad phase II clinical development programme. It is administered as an oral capsule and taken once per day. Ongoing clinical trials are investigating bemcentinib in COVID-19, and multiple solid and haematological tumours, in combination with current and emerging therapies (including immunotherapies, targeted therapies and chemotherapy), and as a single agent. Bemcentinib targets and binds to the intracellular catalytic kinase domain of AXL receptor tyrosine kinase and inhibits its activity.

On March 5, 2021 Corvus Pharmaceuticals, Inc. (NASDAQ: CRVS), a clinical-stage biopharmaceutical company, reported that the Company’s management will participate in two upcoming investor conferences in March (Press release, Corvus Pharmaceuticals, MAR 5, 2021, View Source [SID1234576185]):

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The first conference will be the H.C. Wainwright Global Life Sciences Conference, which is taking place March 9-10, 2021. The Company will conduct one-on-one meetings with institutional investors at this conference and a pre-recorded corporate overview presentation by Richard A. Miller, M.D., president and chief executive officer of Corvus, will be available to play on-demand starting at 7:00 am ET on Tuesday, March 9.

The second conference will be the 33rd Annual Roth Virtual Conference, which is taking place March 15-17, 2021. Dr. Miller will participate in a fireside chat at 2:30 pm ET / 11:30 am PT on Tuesday, March 16 and the Company will conduct one-on-one meetings with institutional investors at the conference. In addition, a pre-recorded corporate overview presentation by Dr. Miller will be made available beginning on Monday, March 8, 2021.
A webcast of the presentations and the fireside chat noted above will be available via the investor relations section of the Corvus website and replays will be available for 90 days following the events.

On March 5, 2021 Bristol Myers Squibb reported FDA’s recent approval for Breyanzi, a new pharma giant is entering the CAR-T lymphoma fray (Press release, FiercePharma, MAR 5, 2021, https://www.fiercepharma.com/pharma/ready-to-square-off-bms-breyanzi-novartis-exec-says-he-s-welcoming-car-t-competition [SID1234576175]). But with new, impressive real-world data and a global manufacturing expansion under its belt, rival Novartis says it’s ready to rumble.

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Novartis last year opened CAR-T production sites in Switzerland and France, while a partner opened a facility in Japan. Another partner, Cell Therapies, has since opened the first CAR-T manufacturing site in Australia. Now, the Swiss drugmaker can call on seven CAR-T manufacturing sites on four continents.

That’s a major advance, particularly after Novartis struggled with Kymriah supplies early on—and given the notorious difficulties that come with producing CAR-T treatments. With the new production sites, the company is "able to meet global demands." said Stefan Hendriks, Novartis’ global head of cell and gene therapies.

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Now, Bristol’s Breyanzi is entering the fray. The medicine won an FDA approval early last month, and a BMS exec contends the drug carries a "differentiated" profile featuring "rapidly occurring responses" and "durable responses."

But Novartis has 5-year data to spotlight—the longest follow-up data for an FDA-approved personalized lymphoma cell therapy, the researchers said. And the data show Kymriah delivers durable responses as well.

Among 24 Kymriah patients with diffuse large B-cell lymphoma, 46% were in complete remission and 31% achieved progression-free survival at five years, researchers with Penn’s Abramson Cancer Center reported last month. And among 14 patients with relapsed or refractory follicular lymphoma, 71% were in complete remission at five years. Forty-three percent of the relapsed/refractory follicular lymphoma patients achieved progression-free survival at five years.

The data show Kymriah is becoming "more and more proven in the real world," Hendriks said in an interview this week.

Novartis won the industry’s first FDA approval for a CAR-T therapy back in August 2017, when the agency endorsed Kymriah to treat a rare form of acute lymphoblastic leukemia. Gilead’s Yescarta scored an approval in relapsed or refractory large B-cell lymphoma a couple of months later, giving the Gilead drug a first-to-market advantage in the larger patient group. The following May, Novartis’ drug scored an FDA approval to match its rival in relapsed or refractory large B-Cell lymphoma.

CAR-T drugs are created using a patient’s own T cells, which are extracted, genetically modified and then infused back into patients to help the body kill cancer cells. Because of the complex nature of the process, manufacturing and logistics are key considerations for companies working to supply those treatments.

Novartis had some Kymirah supply problems early on. In late 2018, the company acknowledged some doses were not meeting quality specifications, and that it was giving them away to patients and doctors who asked. At the time, a spokeswoman said the company was "making improvements to our manufacturing process to increase efficiency and reduce variability."

RELATED: Novartis fills manufacturing gap for CAR-T therapy Kymriah with first Asian production facility

Now, with the supply wrinkles shaken out, around 290 sites worldwide are administering the drug, Hendriks said, and the drug is reimbursed in 27 countries.

Aside from that real-world data, other evidence has shown that a significant number of Kymriah patients can be treated in the outpatient setting, meaning they don’t have to stay in the hospital for long periods of time, Hendriks said. That’s "very beneficial" during the pandemic and has been "recognized" by doctors, he added. As a result, the company’s "market share has nicely grown" during the pandemic, Hendriks said.

Still, on the sales front, the company has some catching up to do against Gilead’s Yescarta. Gilead’s drug pulled in $563 million worldwide last year, while Novartis’ Kymriah generated $474 million. Moving forward, the third entrant from Bristol Myers Squibb will be wrestling for share.

Even though Novartis has been in cell therapy for years, Hendriks says it’s still early days for the field. The CAR-T class is still only reaching 20% of eligible patients, he said, and as more drugs launch, awareness among doctors and patients will grow. The Novartis exec said he’s "welcoming competition" as Novartis and others work to expand the reach for their medicines.

RELATED: Bristol Myers’ Breyanzi tunes its pitch for fight against entrenched CAR-T players Novartis and Gilead

Down the road, he sees the current generation of CAR-T therapies moving into earlier lines of treatment and fighting more cancers, including multiple myeloma. The Novartis exec also sees next-gen manufacturing platforms producing the drugs faster and more efficiently.

On March 5, 2021 Celldex Therapeutics, Inc. (Nasdaq:CLDX) reported the Company’s participation in a fireside chat at the H.C. Wainwright Global Life Sciences Conference (Press release, Celldex Therapeutics, MAR 5, 2021, View Source [SID1234576170]). The presentation for the virtual conference was prerecorded and will be accessible to conference attendees starting on Tuesday, March 9th 2021 at 7:00 a.m. ET.

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A webcast of the presentation will be available on the "Events & Presentations" page of the "Investors & Media" section of the Celldex website. A replay will be available for fourteen days following the event.

On March 5, 2021 BioEclipse Therapeutics (BioEclipse), a private clinical-stage biopharmaceutical company with a proprietary platform for developing next-generation cancer immunotherapies, reported the administration of the first dose of CRX100 to a volunteer in the ongoing Phase 1 clinical trial in patients with refractory solid tumors (Press release, BioEclipse Therapeutics, MAR 5, 2021, View Source [SID1234576163]). The trial is a first-in-human study for CRX100, BioEclipse’s lead investigational drug candidate, an intravenously delivered, multi-mechanistic therapy designed to target and destroy multiple cancer types and address disease recurrence.

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The trial volunteer was administered a single dose of CRX100 at the HonorHealth Research Institute in Scottsdale, Ariz., one of two trial sites participating in a Phase 1, open-label, dose-escalation study exploring the safety, tolerability, and pharmacokinetic (PK) properties of CRX100 in patients with advanced solid tumors not responding to standard of care therapy. The study will enroll up to 24 participants ­18 years or older and specifically target six potential cancer indications, including: triple-negative breast cancer, colorectal cancer, hepatocellular carcinoma, osteosarcoma, epithelial ovarian cancer, and gastric cancer. As secondary endpoints, the trial will also investigate the effect CRX100 has on a participant’s tumor progression and overall immune response.

More information about this study and general information about participating in clinical trials can be found at ClinicalTrials.gov and on our website at www.bioeclipse.com.

"With the first patient now dosed in our Phase 1 trial, we have crossed an important milestone in furthering the clinical development of CRX100, which we believe has enormous potential as a single therapeutic designed to launch a multi-mechanistic attack against multiple cancer types," stated Pamela Contag, Ph.D., President and CEO of BioEclipse. "The need for more effective treatment options, especially for patients with cancers refractory to standard therapies is both urgent and unmet. With enrollment now underway at three clinical trial sites, we look forward to reporting top line data later this year."

BioEclipse is currently focused on the treatment of recurring cancers. CRX100 was developed with technology exclusively licensed from Stanford University that combines activated immune cells, known as cytokine-induced killer (CIK) cells, with an oncolytic virus. As stand-alone agents, these two components have previously been assessed in human studies. When combined to create CRX100, the CIK cells are expected to protect the oncolytic virus and deliver it to cancer cells throughout the body. The two components are intended to work together to attack primary tumors and metastatic disease. Data from preclinical studies shows that this combination approach may also trigger a long-lasting immune response that protects against relapse and disease recurrence.

BioEclipse will collaborate with Seattle-based C3 Research Associates, a contract research firm providing clinical trial management, clinical monitoring, medical monitoring, biostatistics and data management, pharmacovigilance, as well as data monitoring for the clinical trial.

"We at C3 Research are excited to be part of this incredible study team," stated Ron Carozza, CEO and Director of Clinical Operations for C3 Research. "The dosing of the first patient is an important milestone in the clinical development of an exciting new potential therapy for cancer patients. None of this would be possible without the hard work of the project team, the clinic staff and, of course, our study participants."