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.

On December 22, 2021 DURECT Corporation (Nasdaq: DRRX) reported a licensing agreement granting Innocoll Biotherapeutics plc, a specialty pharmaceutical company and portfolio business of Gurnet Point Capital, exclusive development and commercialization rights to POSIMIR (bupivacaine solution) for infiltration use, DURECT’s FDA-approved non-opioid, sustained-release local analgesic for the treatment of post-surgical pain in adults following arthroscopic subacromial decompression surgery, in the United States (Press release, DURECT, DEC 22, 2021, https://investors.durect.com/news-releases/news-release-details/durect-and-innocoll-announce-136-million-us-licensing-agreement [SID1234597622]).

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"We are excited to license the U.S. development and commercialization rights for POSIMIR to Innocoll, whose dedicated hospital sales and marketing organization is deeply committed to providing non-opioid analgesia products to patients in the post-surgical setting," said James E. Brown, President and Chief Executive Officer of DURECT Corporation. "Completing this POSIMIR deal is another important step in the continued transformation of DURECT as we continue to focus on larsucosterol, our lead epigenetic regulator, which is in late-stage clinical development for alcohol-associated hepatitis."

"We believe that POSIMIR has the potential to become a cornerstone of multi-modal post-operative pain management as well as an important contributor to the on-going efforts to provide safe and effective alternatives to opioid-based medications following surgery," added Louis Pascarella, Chief Executive Officer of Innocoll. "Innocoll is now the only company with two bupivacaine-based, sustained-release, non-opioid products, that are FDA approved and indicated for relief of post-surgical pain in specified surgical procedures. We are currently on track to launch POSIMIR in the second quarter of 2022, subject to commercial supply timelines."

Terms of the Collaboration

Under the terms of the agreement, Innocoll will make near-term payments to DURECT of $6 million, consisting of a $4 million license fee and a $2 million payment upon first commercial sale, with the potential for up to an additional $130 million in commercial, regulatory and intellectual property milestone payments as well as tiered, low to mid double-digit royalties on net product sales in the United States.

Innocoll has been granted the exclusive right to develop and commercialize POSIMIR in the United States. Innocoll has also been granted the right to conduct additional development activities to expand the approved indications for POSIMIR, and DURECT’s contract manufacturing supply agreement for POSIMIR has been assigned to Innocoll. DURECT retains all commercial rights to POSIMIR throughout the rest of the world.

Conference Call

DURECT will host a conference call today to discuss the license agreement with Innocoll:

View Source

The conference call will also be available by webcast on DURECT’s homepage at www.durect.com under the "Investors" tab. If you are unable to participate during the webcast, the call will be archived on DURECT’s website under "Event Calendar" in the "Investors" section.

On December 22, 2021 Agenus (NASDAQ: AGEN), an immuno-oncology company with an extensive pipeline of checkpoint antibodies, adjuvants, and vaccines designed to activate immune response to cancers and infections, reported the publication of results in the Journal of Clinical Oncology (JCO) from a global Phase 2 clinical study of balstilimab (Bal) plus zalifrelimab (Zal) in second-line (2L) recurrent/metastatic cervical cancer patients who had relapsed after treatment with platinum-based therapy (Press release, Agenus, DEC 22, 2021, View Source [SID1234597621]).

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"We’re excited to present this data from the largest study conducted to date, assessing the benefit from combined PD-1 and CTLA-4 inhibition in this patient population," said Steven O’Day, MD, Chief Medical Officer of Agenus. "The combination data with Bal (anti-PD-1) and Zal (anti-CTLA-4) in recurrent/metastatic cervical cancer represents a meaningful improvement over currently available therapies while demonstrating a well-tolerated safety profile. We are committed to pursuing the benefit of combination therapies with first-generation antibodies like Zal as well as with our next-generation candidates which include our Fc-enhanced anti-CTLA-4 antibody AGEN1181."

The trial showed that in the 125 evaluable patients treated with Bal/Zal, ORR was 25.6%; among PD-L1+ patients, the ORR was 32.8%. The Phase 2 trial was conducted in patients with recurrent/metastatic cervical cancer who had relapsed after prior platinum-based therapy, a population disproportionately represented by younger women, who have limited effective treatment options. Complete and partial responses were achieved by 8.0% and 17.6% of all patients respectively. The disease control rate in the trial was 52.0%. Responses achieved in patients were highly durable, with a median duration of response not yet reached (NR) following 21-month median follow-up (95% CI: 9.7 months to NR). Median overall survival was 12.8 months, with 69.2% and 53.3% of patients remaining alive at 6 and 12 months, respectively. Responses were observed across tumor histologies in the trial.

"With durable responses and a well-tolerated safety profile, the combined inhibition of PD-1 and CTLA-4 is a much-needed option for patients in this setting," said David O’Malley, MD, lead study investigator; Professor and Director of the Division of Gynecologic Oncology, The Ohio State University – James Cancer Center.

The Bal/Zal combination continued to show no unexpected toxicities and no new safety signals were identified. TRAEs leading to discontinuations occurred in 7.7% of patients.

About Cervical Cancer
Cervical cancer is a malignancy that originates in the cervix, the lower part of the uterus. It is the fourth most common cancer diagnosed among women globally, with nearly 14,500 patients expected to be diagnosed in the U.S. alone in 2021. Cervical cancer disproportionately affects younger women and is most frequently diagnosed between the ages of 35 to 44 in the U.S., with the average age at diagnosis being 50. Despite preventable measures such as HPV vaccination and early pap-smear that exist for prevention and early detection of disease, over 50% of cervical cancer cases in the U.S are only detected after the disease has spread. In patients whose disease has spread to distant parts of the body, 5-year survival rate in the U.S. is estimated to be 17%. Nearly 4,300 women are expected to die from cervical cancer in the U.S. in 2021.

About Balstilimab
Balstilimab is a novel, fully human monoclonal immunoglobulin G4 (IgG4) designed to block PD-1 (programmed cell death protein 1) from interacting with its ligands PD-L1 and PD-L2. PD-1 is a negative regulator of immune activation that is considered a foundational target within the immuno-oncology market.

About Zalifrelimab
Zalifrelimab is a novel, fully human monoclonal immunoglobulin G1 (IgG1) designed to block CTLA-4 (cytotoxic T-lymphocyte associated antigen 4) from interacting with its ligands CD80 and CD86. CTLA-4 is a negative regulator of immune activation that is considered a foundational target within the immuno-oncology market.

On December 22, 2021 Allarity Therapeutics, Inc. ("Allarity" or the "Company") (Nasdaq: ALLR) reported the submission of a new drug application (NDA) with the U.S. Food and Drug Administration (FDA) seeking marketing approval for dovitinib for the third-line treatment of renal cell carcinoma (RCC) patients (Press release, Allarity Therapeutics, DEC 22, 2021, View Source;U.S.-FDA-for-Dovitinib-for-Third-Line-Treatment-of-Renal-Cell-Carcinoma-RCC/default.aspx [SID1234597618]).

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The Company’s NDA filing is supported by its prior PMA submission with the FDA for use of Dovitinib-DRP, the Company’s validated companion diagnostic for the drug, to select and treat RCC patients most likely to respond to dovitinib.

Allarity’s CEO Steve Carchedi noted, "This NDA submission for dovitinib, in connection with the Dovitinib-DRP companion diagnostic, is a historic milestone for our Company and an important step for late-stage renal cell carcinoma patients awaiting new treatment options. Over the past decade, we have worked diligently to advance our novel oncology therapeutics pipeline together with our unique DRP diagnostic technology to realize the promise of personalized cancer care for patients. We greatly look forward to the approval of dovitinib and to introducing the clinical value of DRP companion diagnostics to oncologists and their patients."

Dovitinib is a small molecule, pan-tyrosine kinase inhibitor in-licensed from Novartis, and is Allarity’s most advanced clinical therapeutic candidate. The drug has previously shown clinical activity in a number of cancer indications, including RCC, gastrointestinal stromal tumors (GIST), endometrial cancer, metastatic breast cancer, and hepatocellular carcinoma (HCC). The Company expects to further evaluate the therapeutic benefit of dovitinib in one or more of these additional indications, either as a monotherapy or in combination with other oncology therapeutics.

"As a clinical oncologist looking for new therapies for my RCC patients, I am enthusiastic about Allarity’s NDA filing together with its Dovitinib-DRP(R) companion diagnostic," stated Professor Roberto Pili, M.D., Associate Dean for Cancer Research and Integrative Oncology at the University at Buffalo Jacobs School of Medicine and Biomedical Sciences. "These patients, and their treating oncologists, are greatly in need of new precision medicines, coupled with validated companion diagnostics, to help select and treat the most likely responders. I look forward to working with Allarity to advance this new personalized cancer care approach for RCC patients."

Allarity’s unique and clinically-validated DRP companion diagnostics platform enables the prediction of whether a particular cancer patient is likely to respond to treatment with dovitinib, in addition to a broad range of anti-cancer drugs. DRP drug response assessments for an individual patient are made based on a biopsy from the patient’s tumor. The Dovitinib-DRP companion diagnostic is intended to be used to identify patients with later-stage renal cell carcinoma (RCC) who, by the gene expression signature of their tumor, are identified as having a high likelihood of responding to dovitinib. By identifying and treating only those RCC patients most likely to respond to dovitinib, and avoiding treatment of those RCC patients likely to not respond to the drug, Allarity aims to improve treatment options for patients and their treating oncologist to improve therapeutic benefit.

On December 22, 2021 Novartis reported that it entered into a definitive agreement to acquire all of the outstanding share capital of the UK-based ocular gene therapy company Gyroscope Therapeutics (Press release, Novartis, DEC 22, 2021, View Source [SID1234597617]).

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Geographic atrophy (GA) is an advanced form of dry age-related macular degeneration (AMD) that leads to progressive and irreversible vision loss1. There are no approved treatments for GA, making it one of the most significant unmet needs remaining in retinal diseases2.

GT005 is designed as an AAV2-based, one-time investigational gene therapy for GA secondary to AMD that is delivered under the retina. GT005 aims to restore balance to an overactive complement system, a part of the immune system, by increasing production of the CFI protein. Complement overactivation can lead to inflammation that damages healthy tissues, and it has been strongly correlated with the development and progression of AMD3. The CFI protein regulates the activity of the complement system. It is believed that increasing CFI production could reduce inflammation, with the goal of preserving a person’s eyesight.

The safety and efficacy of GT005 for the treatment of GA secondary to AMD is currently being evaluated in a Phase 1/2 clinical trial and two Phase 2 clinical trials4,5,6. GT005 has received Fast Track designation from the U.S. Food and Drug Administration for the treatment of people with GA.

Gyroscope also has several additional assets in its pipeline in early discovery for retinal diseases.

"With our own pioneering research in ocular gene therapies and our experience gained from bringing Luxturna to inherited retinal dystrophy patients outside of the US, Novartis has a well-established expertise in ocular gene therapies that will position us well to continue developing this promising one-time treatment" said Marie-France Tschudin, President, Novartis Pharmaceuticals. "This acquisition is one more step forward in our commitment to delivering innovation in ophthalmology to treat and prevent blindness worldwide."

Novartis will make an upfront payment of $800 million and potential additional milestone payments of up to $700 million. Closing of the transaction is subject to customary closing conditions including regulatory approvals. Until closing, Novartis and Gyroscope Therapeutics will continue to operate as separate and independent companies.

About geographic atrophy (GA)
Dry AMD is a leading cause of permanent vision loss in people over the age of 55 and is a devastating diagnosis2,7. As dry AMD advances, it leads to GA, an irreversible degeneration of retinal cells, causing a gradual and permanent loss of central vision. This disease can severely impact a person’s daily life as they lose the ability to drive, read and even see faces7.