On March 26, 2024 Enveric Biosciences (NASDAQ: ENVB) ("Enveric" or the "Company"), a biotechnology company dedicated to the development of novel neuroplastogenic small-molecule therapeutics for the treatment of depression, anxiety, and addiction disorders, reported a corporate update and provided financial results for the fourth quarter of 2023 and fiscal year ended December 31, 2023 (Press release, Enveric Biosciences, MAR 26, 2024, View Source [SID1234641445]).

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 fourth quarter of 2023 and early 2024 was a significant period for Enveric, highlighted by the selection of EB-003 as our lead development candidate. We believe EB-003 is a groundbreaking, neuroplastogen drug candidate that offers the potential to treat severe mental health disorders without the hallucinogenic effect typically associated with psychedelic-based molecules," said Joseph Tucker, Ph.D., Director and CEO of Enveric. "Based on numerous discussions with large pharmaceutical companies, mental health professionals, and leading researchers, we believe it is evident that widespread market acceptance of psychedelic-inspired drugs will ultimately be determined by the ability to administer such medications in an outpatient setting. We believe minimizing the hallucinatory effect will be key to seizing this opportunity and was critical in our decision to select EB-003 as our lead product candidate of the EVM301 series. We now look forward to advancing preclinical activities in early 2024 in support of filing an IND for EB-003 as we seek to introduce a new treatment paradigm for depression and anxiety disorders."

Dr. Tucker continued, "The decision to designate EB-003 as our lead candidate was the culmination of an extensive design and evaluation process. This effort included the creation of more than one thousand compounds around which we have built a substantial intellectual property estate, increasing the attractiveness of these molecules for further development. Already in 2024, we have seen returns on this strategy in the form of out-licensing agreements as partners recognize the value of our innovative compounds that are protected with strong intellectual property and have the potential to exapand therapeutic options for patients with depression and anxiety. We will attempt to pursue additional out-licensing and partnership opportunities throughout the year as we continue to advance discussions with multiple possible partner companies."

Dr. Tucker concluded, "During the fourth quarter, we also continued to progress IND-enabling preclinical work for EB-002, completing important repeat-dose toxicology studies, genotoxicity studies, as well as cardiac, respiratory markers, and CNS safety pharmacology studies. We expect to finalize all preclinical activities for EB-002 soon, making the asset Phase 1 ready in 2024."

FOURTH QUARTER AND YEAR END UPDATES

Pipeline Advances and Highlight

Selected EB-003 as lead drug candidate from the Company’s next-generation EVM301 Series based on the molecule’s pharmacological properties and it’s potential to be a first-in-class treatment that addresses difficult-to-treat mental health disorders.
Presented two posters at the 6th Neuropsychiatric Drug Development Summit and two posters at the Canadian Chemical Engineering Conference (CSChE 2023) providing an update on the Company’s near-term selection EB-003 and highlighting key preclinical examinations of EB-002, a novel prodrug of psilocin.
Published cover article in the Journal of Medicinal Chemistry, a peer-reviewed journal published by the American Chemical Society, describing the development EB-002.
Progressed preclinical development of psilocin prodrug, EB-002, with GLP-toxicology and safety pharmacology studies, repeat dose toxicology studies, as well as cardiac, respiratory, CNS safety pharmacology studies, an in vitro hERG current study, and genotoxicity studies.
Expanded Business Development and Out-Licensing Opportunities in 2023 and 2024

Signed three non-binding term sheets with an undisclosed biotechnology company to pursue the out-licensing of three classes of compounds; future development and sales milestone payments and execution fees for the three licenses could total up to $200 million.
Signed two non-binding term sheets with a second undisclosed biotechnology company to pursue the out-licensing of cannabinoid conjugate compounds for pharmaceutical and non-pharmaceutical applications for the treatement of joint diseases; future development and sales milestone payments and execution fees for the two licenses could total up to $61 million.
Surpassed one thousand synthesized compounds discovered and characterized in our PsybraryTM portfolio of novel psychedelic-inspired molecules, following the acceleration of our AI-backed platform tailored for specific applications in the management of mental health disorders.
Continued to strengthen our intellectual property portfolio, receiving ten patent issuances from the United States Patent and Trademark Office.
FOURTH QUARTER AND FISCAL YEAR ENDED 2023 FINANCIAL RESULTS

Net loss attributable to stockholders was $3.44 million for the fourth quarter ended December 31, 2023, including $1.48 million in net non-cash expense, with a basic and diluted loss per share of $1.46, as compared to a net loss of $8.80 million, including $4.48 million in net non-cash expense, with a basic and diluted loss per share of $4.89 for the quarter ended December 31, 2022.

On December 28, 2023, the Company completed a warrant inducement transaction with two investors in which existing warrants were repriced and exercised and new warrants were issued to the investors. The cash proceeds from that transaction were received on January 4, 2024. Subsequently, on February 29, 2024, approximately 90% of the new warrants were also exercised. The gross proceeds to the Company from the two warrant exercises totaled approximately $4.5 million.

On March 26, 2024 Domain Therapeutics ("Domain" or "the Company"), a global clinical-stage biopharmaceutical company developing innovative drug candidates in immuno-oncology targeting G Protein-Coupled Receptors (GPCRs), reported that latest preclinical data on DT-9045, a novel protease-activated receptor 2 (PAR2) Negative Allosteric Modulator candidate, will be presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2024 in San Diego, California (Press release, Domain Therapeutics, MAR 26, 2024, View Source [SID1234641444]).

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!

Date/Time: 7 April 2024 1:30 PM – 5:00 PM PST – Section 27
Abstract number: 684 / 30
Poster session: PO.ET09.05 – Novel Antitumor Agents 2
Title: DT-9045, a novel PAR2 inhibitor with best-in-class properties that reduces resistance to both EGFR-targeting therapies and immunotherapy in oncology models
The abstract will be made available in the online Proceedings of the AACR (Free AACR Whitepaper).

PAR2 is one of the genes most significantly linked to resistance against immune checkpoint blockage (ICB) and T cells dysfunction in cancer patients. Its upregulation across a variety of cancer types and expression on diverse cells within the tumor microenvironment underscore PAR2’s critical role in cancer development.

Leveraging its integrated precision research approach, backed by over 20 years of solid GPCR expertise, Domain has developed a novel highly potent and selective PAR2 inhibitor, DT-9045. This first-in-class Negative Allosteric Modulator has shown unparalleled potential in oncology and immuno-oncology. Remarkably, when compared to its most advanced competitors positioned in other therapeutic areas, this candidate has demonstrated clear differentiated features. Moreover, several proof-of-concept studies have shown strong potency in models resistant to EGFR-targeting therapies and immunotherapy opening solid perspectives of strategic clinical positioning and revenues generation in tumor types that constitute a high medical unmet need.

DT-9045 is a small molecule, orally available, insurmountable, biased, and active in tumor-like conditions (high concentration of activating proteases and acidic pH). IND-enabling studies are currently ongoing to advance the candidate toward the clinic.

Stephan Schann, Chief Scientific Officer of Domain Therapeutics, commented: "We are excited to present our newest findings on DT-9045 at AACR (Free AACR Whitepaper). The results not only confirm the immense potential of our PAR2 inhibitor to change the way we treat cancer, but also emphasize its high potency and efficacy against several drug resistance, offering cancer patients clear therapeutic perspectives in immuno-oncology. More broadly, they reflect our deep commitment to precision research, pioneering innovative new GPCR targets in immunosuppression, designing clear competitive properties to deliver game-changing candidates. We eagerly anticipate advancing this groundbreaking research, with a focus on addressing a substantial unmet medical need for cancer patients."

This progress, follows the announcement in June 2023 when DT-9045 was nominated as a first-in-class clinical PAR2 antagonist. It has shown great therapeutic potential in enhancing the efficacy to immunotherapy aiming to substantially improve treatment outcomes for non-responding cancer patients.

On March 26, 2024 Delcath Systems, Inc. (Nasdaq: DCTH) ("Delcath" or the "Company"), an interventional oncology company focused on the treatment of primary and metastatic cancers of the liver, reported recent business highlights and financial results for the fourth quarter and full year ended December 31, 2023 (Press release, Delcath Systems, MAR 26, 2024, View Source [SID1234641443]).

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!

Recent Business Highlights
During and since the fourth quarter, Delcath:

Announced the first commercial use of HEPZATO KIT for the treatment of metastatic uveal melanoma (mUM) at Moffitt Cancer Center;
Activated three treating sites which are fully trained to treat commercial patients with a fourth expected to be active before the end of the first quarter and an additional three sites expected to become active in the first few weeks of the second quarter of 2024;
Updated site activation guidance from 15 active sites to a total of 20 active sites by the end of 2024;
Received notification that a permanent, product-specific J-code (J9248) and transitional pass-through payment status for HEPZATO, was established by the Centers for Medicare & Medicaid Services (CMS) and will become effective on April 1, 2024;
Finalized its patient access program and launched websites relating to the HEPZATO KIT, including HEPZATOKIT.com, HEPZATOKITREMS.com, and HEPZATOKITACCESS.com, to support the commercial launch;
Raised $7.0 million in a private placement transaction with certain accredited investors comprised of existing investors, Delcath senior executives, and members of its Board of Directors;
Appointed Martha S. Rook, Ph.D as Chief Operating Officer on March 18, 2024. Ms. Rook is an experienced industry leader who brings more than 25 years of academic and industry experience in molecular biology, diagnostics development, biologics process development and combination products manufacturing; and
Announced publication by independent investigators of:
A retrospective comparative study of CHEMOSAT Hepatic Delivery System for Melphalan percutaneous hepatic perfusion (PHP) and Selective Internal Radiation Therapy (SIRT) citing a statistically significant difference in median overall survival with 301 days for SIRT and 516 days for PHP; and
A clinical study entitled "Quality of Life After Melphalan Hepatic Perfusion for Uveal Melanoma" in which the authors concluded utilizing Delcath’s CHEMOSAT to administer high-dose melphalan to the liver is well tolerated by patients and does not negatively affect their quality of life.
"We have made tremendous progress since the January launch of HEPZATO KIT in the US," said Gerard Michel, Delcath’s Chief Executive Officer. "We have successfully secured a product specific J-Code and, with over 90 preceptorships completed by healthcare professionals across approximately 20 institutions in the US, are on track to train and activate 20 sites by year end. Furthermore, we have strengthened our balance sheet with additional investment from senior management and existing investors. I am proud of the team’s success in providing access to a new treatment for patients suffering from metastatic uveal melanoma."

Fourth Quarter and Full Year 2023 Results
Cash, cash equivalents and investment totaled $32.5 million as of December 31, 2023. Subsequent to year-end, on March 19, 2024, the company closed a $7.0 million private placement financing.

Total revenue for the quarter and year-ended December 31, 2023, was approximately $0.5 million and $2.1 million, respectively, compared to $0.6 million and $2.7 million for the same periods in the prior year, respectively, from our sales of CHEMOSAT in Europe.

Research and development expenses for the quarter and year-ended December 31, 2023, were $4.7 million and $17.5 million, respectively, compared to $4.4 and $18.6 million, respectively, for the same periods in the prior year. The change in research and development expenses is primarily due to a decrease in clinical trial activities and expenses related to the FDA inspection offset by an increase in personnel related expenses.

Selling, general and administrative expenses for the quarter and year-ended December 31, 2023, increased to $7.0 million and $22.1 million, respectively, compared to $3.8 million and $17.3 million, respectively for the same periods in the prior year. The increase primarily relates to activities to prepare for a commercial launch including marketing-related expenses and additional personnel in the commercial team.

On March 26, 2024 Defence Therapeutics Inc. ("Defence" or the "Company"), (CSE: DTC, OTCQB: DTCFF, FSE: DTC), a Canadian biotechnology company developing novel immune-oncology therapeutics and drug delivery technologies, reported the successful testing of a second-generation anti-cancer vaccine, called ARM-002TM, using its lead anti-cancer molecule AccuTOX (Press release, Defence Therapeutics, MAR 26, 2024, View Source;utm_medium=rss&utm_campaign=defences-successful-results-on-its-accutox-anti-cancer-armtm-vaccine-creates-a-potent-second-generation-anti-cancer-arm-002tm-vaccine [SID1234641442]). When tested as a therapeutic vaccine in a melanoma cancer model, ARM-002TM leads to an 80% complete response when combined with the anti-PD-1 immune-checkpoint inhibitor.

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!

Compared to current anti-cancer strategies, vaccination can stimulate specific immune responses capable of potentially curing established tumors. In addition, developed immune cells can lead to a long-lasting memory response capable of further protecting the patient from subsequent cancer relapses. Using mesenchymal stromal cells (MSCs) as a vaccination platform; Defence has previously shown that it is possible to pharmacologically reprogram these immune-suppressive cells into potent antigen presenting cells using its Accum derivative called A1 (ARMTM vaccine). Although the ARMTM vaccine can effectively present antigens to responding T cells, the large amount of antigen preparation required to generate the cellular vaccine might represent challenges in the clinic. Defence elected to test its lead AccuTOX molecule to engineer a second-generation anti-cancer vaccine as the latter was shown to directly enhance antigen presentation in cancer cells if delivered intratumorally at lower doses.

"AccuTOX is an amazing molecule! AccuTOX has the capacity to trigger cancer cell death when used as a direct cancer injectable, and AccuTOX, the same molecule, converts MSCs into potent antigen presenting cells capable of priming potent anti-tumoral responses using a 10-fold lower antigen preparation" says Mr. Plouffe, Chief Executive Officer of Defence Therapeutics.

The ARM-002TM vaccine was tested in vivo in the context of melanoma. The vaccine elicited an impressive anti-tumoral response, which prompt the team to widen its scope of application by further testing it on "hard to treat" ovarian and pancreatic cancers. The Defence team are conducting additional studies in parallel to decipher the exact mode of action of AccuTOX in reprograming MSCs while studying the mechanistic behind the ARM-002TM potency using different in vivo studies. Once these studies finalized and the "Dry Run" manufacturing of the ARM-002TM vaccine completed, a request to obtain clearance for a Phase I trial targeting a basket of solid tumors will be initiated.

Data Bridge Market Research analyses that the solid tumours market was valued at $209.61-billion (U.S.) in 2021 and is expected to reach $901.27-billion (U.S.) by 2029, registering a CAGR (compound annual growth rate) of 20 per cent during the forecast period of 2022 to 2029.

View Source,period%20of%202022%20to%202029.

On March 26, 2024 Curve Therapeutics ("Curve" or the "Company"), a private biotechnology company pioneering a revolutionary intracellular screening platform addressing complex and challenging disease targets, reported the publication of an article in the Journal of the American Chemical Society (JACS) (Press release, Curve Therapeutics, MAR 26, 2024, View Source [SID1234641440]). The paper entitled ‘Identification and Development of Cyclic Peptide Inhibitors of Hypoxia Inducible Factors (HIF) 1 and 2 That Disrupt Hypoxia-Related Signalling in Cancer Cells’ can be viewed here.1 Curve’s Chief Scientific Officer, Professor Ali Tavassoli, co-authored the article and leads the academic group at the University of Southampton where the work was undertaken.

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!

Professor Ali Tavassoli, Chief Scientific Officer of Curve Therapeutics, said: "It is well recognised that HIF plays a key role in the survival and growth of solid tumours. The compounds we report in this paper inhibit the protein-protein interaction of the two subunits that form the HIF transcription factor. We show that these compounds prevent the hypoxia-induced activity of this transcription factor, stopping hypoxia-response in cell-based assays. This paper underlines the promising therapeutic potential of dual HIF inhibition as an approach for the treatment of a variety of cancers."

Curve Therapeutics is a leader in the discovery of innovative therapeutics to address disease targets which are difficult to target using conventional drug discovery methods. Through the utilisation of its world leading Microcyle discovery platform, Curve can screen directly inside mammalian cells, allowing for the identification of biologically active library members within an intracellular environment where both the library and the target are present in their native conformations. Curve is developing a non-peptidic, small-molecule dual inhibitor of HIF-1 and HIF-2 with first-in-class potential.

This is the first report of a dual HIF-1 and HIF-2 inhibitor which functions by inhibiting the interaction of both HIF-1α and HIF-2α with HIF-1β. The Microcycles discovered by Prof. Tavassoli were identified using his SICLOPPS screening platform and show good cellular activity. Patents and patent applications describing these HIF inhibitory Microcycles are exclusively licensed to Curve.