On November 18, 2022 Candel Therapeutics, Inc. ("Candel" or "the Company") (Nasdaq: CADL), a clinical stage biopharmaceutical company developing novel viral immunotherapies, reported presentation of updated data from a phase 1 clinical trial of CAN-3110 in patients with recurrent high-grade glioma (rHGG) (Press release, Candel Therapeutics, NOV 18, 2022, View Source [SID1234624233]). An overview of this data will be presented in-person at the Society for Neuro-Oncology (SNO) 27th Annual Meeting (SNO) today starting at 5:30 pm ET in Tampa, Florida.

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!

Data will be reported from 41 patients who were administered CAN-3110, with 40 patients having received a single injection and one patient having received two injections. There were no dose-limiting toxicities. The median overall survival was 11.6 months. In-depth biomarker analyses show a statistically significant expansion of activated CD4+ and CD8+ T cells effector cells in multiple tumor lesions following a single injection of CAN-3110. Diversity of the T cell receptor repertoire after CAN-3110 administration was reported to be associated with overall survival. Next, the Company will examine whether multiple injections of CAN-3110 over time could lead to further improvement in overall survival (NCT03152318, clinicaltrials.gov).

"Patients with high-grade glioma whose cancer has recurred following initial standard of care treatments face a daunting challenge, with most succumbing to their disease within months due to a lack of effective therapies," said Paul Peter Tak, MD, PhD, FMedSci, President and Chief Executive Officer of Candel Therapeutics. "We believe CAN-3110 is the first HSV-based viral

immunotherapy candidate designed to leverage the ICP34.5 gene, which plays a key role in the viral anti-host response. The absence of observed dose-limiting toxicities in 41 patients and a median overall survival rate of one year provides clinical validation for this unique construct. This trial has clearly shown that a single injection of CAN-3110 can convert the highly immunosuppressive tumor microenvironment in recurrent high-grade glioma into a ‘hot’ tumor. We are now determining if multiple injections of CAN-3110 can fundamentally transform this universally fatal brain cancer."

CAN-3110 is unique in that it is designed to express a copy of the viral ICP34.5 gene, which is critical for viral replication and anti-host responses, under the transcriptional control of the tumor specific Nestin promoter. This approach is intended to restrict viral replication and virulence to the tumor cells, protecting healthy tissues while maintaining its anti-tumor responses.

Details on the presentation at SNO are as follows:

Oral Presentation Title: Enriched TCR/BCR VDJ rearrangements correlate with MRI and survival outcomes in patients with recurrent high-grade glioma treated with CAN-3110

About CAN-3110

CAN-3110 is a herpes simplex virus (HSV) replication-competent viral immunotherapy candidate engineered to enhance selective killing of malignant cells while sparing healthy normal neighboring cells. CAN-3110 has been shown to selectively express ICP34.5, a key gene in HSV replication, in tumor cells that overexpress Nestin, a cytoskeletal protein. Nestin is highly expressed in glioma cells and other tumor tissue, but is absent in the healthy adult brain. The effects of multiple doses of CAN-3110 in recurrent glioblastoma are currently being evaluated in an ongoing phase 1 clinical trial.

On November 18, 2022 Applied Cells Inc. and GenScript USA Incorporated reported their strategic collaboration to deliver combined cell isolation solutions for cell therapy drug development worldwide (Press release, Applied Cells, NOV 18, 2022, View Source [SID1234624229]). Under this collaboration, GenScript will develop and supply its proprietary research and cGMP grade CytoSinct reagents for use in developing CAR-T and other Cell Therapy products on the Applied Cells MARS Platform.

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!

GenScript has years of experiences on beads development and its own know-how technology on nanoparticle development. Its CytoSinct reagents use perfected nanoparticles, high-quality antibodies and optimized conjugation chemistry to enable high specificity and sensitivity in cell selection. Applied Cells MARS platform utilizes proprietary column-free magnetic separation technology and offers an automated closed-system for the cell selection process. MARS platform provides the Cell Therapy Industry with the long-desired ability to transition from R&D-scale workflow to manufacturing-scale process development with consistent and reproducible performance, and the ability to customize.

Integrating CytoSinct reagents into the MARS platform provides a complete solution of simplified workflow and high-efficiency results for research and industrial-scale cell separation. Both GenScript and Applied Cells will support GMP-compliant documentation for the developed cell therapy products utilizing this innovative solution.

"We are thrilled to collaborate with GenScript in adapting CytoSinct reagents and developing additional clinical grade reagents for use with the MARS Platform," said Dr. Yuchen Zhou, CEO at Applied Cells, "by combining the advantages of the MARS platform and CytoSinct reagents, we bring a more productive, better performance, and low-cost solutions, to meet the evolving customer needs of this rapidly growing field. Our team will work diligently with GenScript colleagues to provide our solutions worldwide, and help expedite the life-saving benefits of cell therapies becoming accessible to everyone."

"GenScript is committed to improving human health. We are honored to cooperate with Applied Cells using our CytoSinct reagents and also develop additional clinical grade reagents for the MARS Platform," said Dr. Hong Qian, the COO of GenScript Life Science Group. "By uniting the strengths of the CytoSinct reagents and the MARS platform, it allows us to work more efficiently and productively, thus providing us the means to reach our goal in the flourishing cell therapy field. We will put our utmost effort into working with Applied Cells to provide our world an alternative solution with lower cost and higher quality in order to benefit human health globally."

On November 18, 2022 G1 Therapeutics, Inc. (Nasdaq: GTHX), a commercial-stage oncology company, reported the pricing of an underwritten public offering of 7,700,000 shares of its common stock at a public offering price of $6.50 per share, for total gross proceeds of $50,050,000 (Press release, G1 Therapeutics, NOV 18, 2022, View Source [SID1234624200]). All of the shares in the offering will be sold by G1 Therapeutics. In addition, G1 Therapeutics has granted the underwriters a 30-day option to purchase up to an additional 1,155,000 shares of common stock at the public offering price, less the underwriting discount. The offering is expected to close on November 22, 2022, subject to customary closing conditions.

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!

Cowen and Raymond James are acting as joint book-running managers for the offering. Needham & Company and Wedbush PacGrow are acting as lead managers for the offering.

The shares are being offered pursuant to a "shelf" registration statement previously filed and declared effective by the Securities and Exchange Commission (the "SEC"). A preliminary prospectus supplement and accompanying prospectus relating to the offering have been filed with the SEC and are available on the website of the SEC at www.sec.gov. Copies of the final prospectus supplement and accompanying prospectus relating to the offering may be obtained, when available, from Cowen and Company, LLC, Attn: Cowen and Company, LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, Attn: Prospectus Department, by telephone: (833) 297-2926 or by email: [email protected]; or from Raymond James & Associates, Inc., Attention: Equity Syndicate, 880 Carillon Parkway, St. Petersburg, Florida 33716, or by telephone at (800) 248-8863, or e-mail at [email protected].

This press release shall not constitute an offer to sell or a solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On November 17, 2022 Bayer reported that new research out of McMaster University found a recently abandoned compound halted the growth of an aggressive form of pediatric medulloblastoma in mouse models (Press release, Bayer, NOV 17, 2022, View Source [SID1234624256]).

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!

Brain tumors have overtaken leukemia as the deadliest childhood cancer. The MYC gene-amplified type of medulloblastoma is the deadliest of the four subgroups, forming highly malignant tumors characterized by therapy resistance and disease recurrence. Even in the cases that are "curable," the cure comes at a steep price for this vulnerable population.

"We often use mortality as our success measure with cancer treatment," William Gwynne, a postdoc at McMaster and first author of the study, told BioSpace.

"Unfortunately, that’s not an accurate measuring stick to how well we’re doing with cancer treatment. Because even though 70% of medulloblastoma patients will be cured with standard of care – chemotherapy and radiation – almost 100% of them will have what we call neurotoxic second delay," he continued. This refers to a series of neurocognitive and developmental deficits.

Gwynne joined Dr. Sheila Singh’s lab for his postdoc training, intrigued by her approach to studying cancer using a comparative developmental biology perspective. Singh is a pediatric neurosurgeon, so this is a need acutely felt in her own patient population.

The Singh Lab team utilized genome-wide CRISPR screening to compare medulloblastoma to neural stem cells.

They identified the genes highly essential for survival of the cancer cells, but non-essential to the stem cells. A collaboration with J. Rafael Montenegro-Burke from the University of Toronto dug into the metabolic profiles of the neural cells versus the medulloblastoma cells. Both the gene research and metabolic research pointed at the same thing, which got the research team "really, really excited."

An Excellent Druggable Target

"It turns out that this enzyme, DHODH, which fuels the production of these pyrimidine molecules, was an excellent druggable target," Gwynne said. "It was being pursued in other cancer types like leukemia. But nobody had pursued this in brain cancer yet."

The team utilized the DHODH inhibitor created by Bayer, BAY2402234, due to its ability to highly penetrate the blood-brain barrier, something other inhibitors like brequinar were unable to do.

The compound had been in a Bayer-sponsored trial for patients with acute myeloid leukemia, but in January the trial was terminated due to "lack of sufficient clinical benefit."

Gwynne pointed to selection of the "right patients" as being the potential key benefit of a DHODH inhibitor. The research zeroed in on a specific set of patients with MYC-driven medulloblastoma because the DHODH pathway is particularly high in those cells. Inhibiting the DHODH in these cells evokes metabolic stress to halt the cycle progression and induce cell death.

An important factor in any new research is reproducibility. Singh and Gwynne’s research was published Nov. 10 in Cancer Cell. In August, two other papers were published in Cancer Cell, one targeting IDH mutant glioma and another studying a near-universally fatal brainstem tumor.

These two papers came to the same conclusion as Singh’s lab. All three teams utilized BAY2402234 to inhibit DHODH for three different kinds of brain cancers, and all signs point to it being a promising approach to stopping brain tumor growth.

Gwynne and Singh are most excited about this potential new treatment approach because of its cancer-targeting effects with minimal impact on healthy cells.

Current, standard treatments like radiation and chemotherapy don’t distinguish between normal and cancer cells. Neurotoxic effects from these therapies leave 40-100% of pediatric brain tumor survivors with cancer-related cognitive impairment.

"It’s just amazing how this is really a cancer-selected metabolic vulnerability," Singh told BioSpace.

Neuro Stem Cells Relatively Untouched

"Only the cancer cells are disabled by this drug. The neuro stem cells are… relatively untouched by the drug at the same dose," she said. This is important because clinical trial subjects are small children with pools of stem cells that are rapidly divided into developing and creating new organs and laying down new pathways in the brain.

"So, it’s absolutely essential that any drug we use doesn’t target those developing cell populations."

In the lab, Gwynne observed how gaunt and sickly the mice treated with chemo and radiation were, as is typical in these studies. In stark contrast, the mice treated with the Bayer compound were "running around the cage happy and healthy." Those mice also outlived the mice receiving traditional treatments.

"This single agent DHODH inhibitor was as effective as current standard of care in this mouse model without the side effects of the mice becoming really, really sick and getting really, really skinny like they normally do," Gwynne said.

Due to the low-toxicity profile, Singh said a Phase I clinical trial is the next logical step. Bayer has yet to contact her, but a lot of interest has surfaced since the paper’s publishing.

"I’ve been contacted by drug developers who are interested and they’re asking me questions like, do you think this could translate to clinical trials?Our papers have reenergized interest around that compound."

On November 17, 2022 Beyond Air, Inc. (NASDAQ: XAIR), a medical device and biopharmaceutical company focused on developing inhaled nitric oxide (NO) for the treatment of patients with respiratory conditions, including serious lung infections and pulmonary hypertension, and, through its affiliate Beyond Cancer, Ltd., ultra-high concentration nitric oxide (UNO) for the treatment of solid tumors, reported that Steve Lisi, Chairman and CEO of Beyond Air, will be presenting a corporate overview and participating in 1×1 meetings at the Piper 34th Annual Healthcare Conference being held November 29 – December 1, 2022 in New York, NY (Press release, Beyond Air, NOV 17, 2022, View Source [SID1234624245]).

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!

If you are interested in requesting a 1×1 meeting at the respective conference, please contact your bank/conference representative. For more details, please see the Events section of Beyond Air’s corporate website.