On December 22, 2021 Advaxis, Inc. (OTCQX: ADXS), a clinical-stage biotechnology company focused on the development and commercialization of immunotherapy products, reported that the Company has satisfied the requirements for trading of the Company’s common stock on the OTCQX Best Market ("OTCQX") and will begin trading on OTCQX at the open of the market on December 23, 2021 under the symbol ADXS (Press release, Advaxis, DEC 22, 2021, View Source [SID1234597669]). The Company previously traded on Nasdaq .

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OTCQX is the top tier of three markets organized by OTC Markets Group Inc. for trading over-the-counter securities, and is designed for established, investor-focused U.S. and international companies. To qualify for the OTCQX market, companies must meet high financial standards, follow best practice corporate governance, demonstrate compliance with U.S. securities laws, and be current with their disclosure. Investors can find current market information and real-time quotes for the Company on www.otcmarkets.com.

On December 22, 2021, Syndax Pharmaceuticals, Inc. (the "Company") reported that it entered into Amendment No. 1 to the Company’s Loan and Security Agreement (the "First Amendment") with the several banks and financial institutions or entities from time-to-time party thereto (collectively, the "Lender") and Hercules Capital, Inc., in its capacity as administrative agent for itself and the Lender (in such capacity, the "Agent") (Filing, 8-K, Syndax, DEC 22, 2021, View Source [SID1234597660]). The First Amendment amended that certain Loan and Security Agreement dated as of February 7, 2020 (the "Existing Loan Agreement," as amended by the First Amendment, the "Loan Agreement") among the Borrower, the Lender and the Agent.

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The First Amendment increases the amount that the Company may borrow by $50.0 million, from up to $30.0 million to up to $80.0 million, in multiple tranches. The First Amendment increases the second tranche ("Tranche 2") from $10.0 million to $30.0 million with $15.0 million being available at the Company’s option through April 30, 2022 and another $15.0 million being available at the Company’s option through November 30, 2022, which availability period will be extended to April 30, 2023 if the first $15.0 million is drawn prior to April 30, 2022. The First Amendment also provides for a third tranche of $30.0 million ("Tranche 3"), which is available, subject to the Agent’s investment committee approval, through the Interest-Only Period (as defined below). The Company’s only borrowings to date under the Loan Agreement are the first tranche of $20.0 million, which the Company drew upon the closing of the Loan Agreement on February 7, 2020.

Additionally, the First Amendment, among other things, (i) extended the expiration of the period in which interest-only payments on borrowings under the Loan Agreement are required from October 1, 2021 to January 1, 2023, which is further extendable to December 31, 2023 upon the partial or full draw of Tranche 2 (the "Interest-Only Period"), (ii) extended the maturity date of Loan Agreement from September 1, 2023 to April 1, 2024, (iii) decreased the annual interest rate from the greater of (w) 9.85% or (x) 5.10% plus the Wall Street Journal prime rate to the greater of (y) 9.25% or (z) 6.00% plus the Wall Street Journal prime rate, (iv) applies a facility charge equal to 0.50% of any future draws, (v) applies a 4.99% end of term charge to any future draws payable on the maturity date, (vi) permits the entry into the Collaboration and License Agreement as previously disclosed with Incyte Corporation, and (vii) adds a minimum cash covenant applicable on the occurrence of certain events. The First Amendment also resets the prepayment premium requirements as of the date of the First Amendment so that any prepayments are subject to a prepayment premium equal to (i) 2.0% of the principal amount outstanding if the prepayment occurs during the first year following the Loan Amendment, (ii) 1.5% of the principal amount outstanding if the prepayment occurs during the second year following the Loan Amendment, and (iii) 1.0% of the principal amount outstanding at any time thereafter but prior to the Maturity Date.

On December 22, 2021 Dovetail Genomics, the industry leader in advanced proximity ligation genomic solutions, reported details of a new study, led by University of Michigan researchers and published in Nature, which showed for the first time that inhibiting the SWI/SNF chromatin remodeling complex prevents several oncogenes from being expressed and slows prostate cancer growth in cell and animal models (Press release, Dovetail Genomics, DEC 22, 2021, View Source [SID1234597627]). These findings were made possible, in part, by Hi-C technology developed by Dovetail Genomics, with the company’s proximity ligation HiChIP MNase Kit providing essential information about 3D chromatin architecture, illuminating the effect the PROTAC had on chromatin remodeling. In addition, Dovetail scientists Mital Bhakta and Jay Ghurye contributed to the paper.

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"This is a revolutionary finding," said Arul Chinnaiyan, M.D., Ph.D., director of the Michigan Center for Translational Pathology and senior author on the paper. "By controlling chromatin structure in prostate cancer cells, we shut down several oncogenic pathways at once. This could offer new hope for patients, particularly those with resistant disease."

Chromatin is the combination of DNA, RNA and proteins that tightly package genetic material in the nucleus. Cells have evolved complex mechanisms, including the SWI/SNF complex, to open up chromatin and allow gene expression.

In the study, the research team designed a proteolysis targeting chimera (PROTAC), a small molecule compound, that degrades SMARCA2 and SMARCA4, essential SWI/SNF components. This degradation had a ripple effect. Inhibiting SWI/SNF kept chromatin closed to cancer-driving transcription factors, which could not reach gene enhancers, muting well-known oncogenes, such as AR (androgen receptor), FOXA1, ERG and MYC.

This work highlights potential therapeutic targets to defeat enhancer-addicted prostate and possibly other cancers. Equally important, PROTAC synergized with the androgen receptor antagonists, which are often used to treat prostate cancer, making them more effective.

"Dovetail has always put an acute focus on cancer research, understanding that proximity ligation takes oncology studies to the next level," said Todd Dickinson, CEO of Dovetail Genomics. "We were thrilled to partner with Dr. Chinnaiyan on this study, helping to identify a critical advance in cancer data and research."

The full article can be found here: View Source

On December 22, 2021 Emendo Biotherapeutics, a next-generation CRISPR biotech expanding the reach of gene editing therapeutics, and Seattle Children’s Research Institute reported a research collaboration to investigate how hematopoietic stem cells (HSCs) extracted from patients with severe congenital neutropenia (SCN) respond to priming treatments ahead of administering a CRISPR-based therapeutic (Press release, Seattle Children Hospital, DEC 22, 2021, View Source [SID1234597626]).

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ELANE-related SCN, also known as SCN1, is a rare, autosomal dominant disease in which a mutation occurs in one allele of the ELANE gene, thereby preventing HSCs from differentiating into white blood cells, specifically neutrophils, which leaves the patient highly susceptible to recurrent bacterial infections, osteoporosis, developmental delays and abnormalities.

"Patients with SCN often suffer from reduced quality of life due to the lack of improvements in the standard of care," said Dr. David Rawlings, Division Chief of Immunology at Seattle Children’s Hospital and Director of the Center for Immunity and Immunotherapies at Seattle Children’s Research Institute. "These children are immunocompromised, and, as a result, we feel a great sense of urgency to ensure we’re exploring all possible avenues towards a solution."

"Seattle Children’s collaboration with Emendo, utilizing its unique approach to edit only the mutated allele with CRISPR, will enable us to address the unmet needs of SCN at the very core," added Rawlings, who also serves as a professor of pediatrics and adjunct professor in the Department of Immunology at the University of Washington School of Medicine. "We’re excited about this opportunity, and look forward to continuing the collaboration beyond this initial study."

Editing the mutated ELANE gene with CRISPR first requires overcoming a technological hurdle: Only the mutated allele must be targeted, while the healthy allele remains intact. Emendo engineered its roster of next-generation CRISPR nucleases to be biologically active and so specific that they can differentiate between two alleles of the same gene. EMD-101, Emendo’s lead therapeutic candidate for SCN, was specifically engineered to target the mutant ELANE allele.

HSCs have been widely studied as a treatment for sickle cell anemia and cancer, as well as a potential therapy to treat organ and tissue damage. However, HSCs require initial priming prior to stem cell transplantation, which is typically done by administering G-CSF (granulocyte colony stimulating factor). Yet, the same drug is also a short-term treatment for SCN patients.

To better understand how SCN patients would respond to a priming dose of G-CSF and plerixafor, Emendo will evaluate the mobilization of HSCs excised from a small group of patients with SCN, which would be gene-edited later. Concurrently, Seattle Children’s will evaluate the composition of the HSCs obtained from the same patients. Prior mouse studies conducted by Emendo have shown that human cells edited to excise the disease-causing ELANE allele sufficiently engrafted and replaced existing diseased cells, restoring proper neutrophil differentiation.

"By combining our allele-specific genome editing technology with Seattle Children’s renowned expertise in SCN — spearheaded by Dr. Rawlings — we are laying the foundation for future clinical trials that could lead to potential therapies to treat the disease," said David Baram, Ph.D., CEO of Emendo. "Our portfolio of engineered nucleases tailored to any gene or allele gives us the unique opportunity to tackle the inherent challenges of SCN. Through this collaboration we’ll be able to provide stronger evidence and further proof points for the capabilities of our technology."

Based on the outcome of the research, a protocol for a clinical trial could be developed with an expected initiation in late 2022, pending regulatory approval. Seattle Children’s has certain preferred rights to serve as a clinical trial site.

On December 22, 2021 CEL-SCI Corporation (NYSE American: CVM) reported financial results for the fiscal year ended September 30, 2021, as well as key clinical and corporate developments (Press release, Cel-Sci, DEC 22, 2021, View Source [SID1234597625]).

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Clinical and Corporate Developments included:

On October 22, 2021, CEL-SCI announced it completed the commercial scale expansion of its dedicated current Good Manufacturing Practice (cGMP) facility in which it manufactures its immunotherapy Multikine (Leukocyte Interleukin, Injection)*. The construction, which began in 2020, was designed to ensure it will be compliant with all requirements of the U.S. Food and Drug Administration’s (FDA) and European cGMP regulations as the facility’s production capacity has been doubled to meet anticipated market demand for Multikine once it receives regulatory approval.
On June 28, 2021, CEL-SCI announced top line results from its 9.5 year global pivotal Phase 3 study for Multikine in head and neck cancer. The Phase 3 results showed a long-term 5-year overall survival (OS) benefit in the treatment arm receiving Multikine treatment regimen followed by surgery and radiation. This survival benefit was statistically significant (two-sided p=0.0236, HR=0.68), robust and durable, with no safety issues, something not commonly seen with cancer drugs. In fact, the survival benefit increased over time and at 5-years the overall survival benefit reached an absolute 14.1% advantage for the Multikine treated arm over control (n=380, total study patients treated with surgery plus radiation): the Multikine treatment arm showed 62.7% overall survival versus the control arm which showed only 48.6% overall survival.
The OS benefit of 14.1% at 5 years for this treatment arm exceeded the 10% OS benefit set out for the study population in the protocol. The results from the Phase 3 cancer study proved that Multikine met all of protocol required benefits stated in the study protocol in patients in the treatment arm receiving surgery and radiation as their standard therapies.
Based on the results of this pivotal Phase 3 study, CEL-SCI intends to file a Biologic License Application with the FDA for approval of the Multikine treatment regimen in advanced primary squamous cell carcinoma of the head and neck patients scheduled to receive surgery and radiation as their primary treatments. CEL-SCI’s trial was conducted in over 20 countries in which marketing clearance applications may also be filed subsequent to FDA filing and/or approval.
CEL-SCI raised net proceeds of approximately $54.1 million during fiscal 2021 through the sale of common stock and the exercise of warrants and options. As of September 30, 2021, CEL-SCI had $42.2 million in cash, cash equivalents and U.S. Treasury Bills.
"Having conducted and completed the largest ever study in head and neck cancer, we are filing for regulatory approval with confidence that Multikine extends life in this severely unmet medical need. Our team has delivered and continues to work hard at preparing our BLA filing, validating and preparing our manufacturing facility for commercial production and publishing our data in peer reviewed journals. With a solid cash runway, we are optimistic about the future and the potential for Multikine to improve the lives of head and neck cancer patients and their families," stated CEL-SCI CEO, Geert Kersten.

CEL-SCI reported a net loss of $36.4 million in fiscal year 2021 versus a net loss of $30.3 million in fiscal year 2020. The increase in net loss was predominantly due to an increase in research and development expenses by approximately $5.3 million, or 30%, and an increase in general and administrative expenses by approximately $1.4 million, or 12%, compared to the year ended September 30, 2020. With the conclusion of the Phase 3 study, the expenditures for fiscal 2022 are expected to be lower.