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]).

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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]).

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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.

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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.

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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.

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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.

On March 26, 2024 bluebird bio, Inc. (NASDAQ: BLUE) ("bluebird bio" or the "Company") reported fourth quarter and annual financial results and business highlights for the year ended December 31, 2023, including recent commercial and operational progress (Press release, bluebird bio, MAR 26, 2024, View Source [SID1234641439]).

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"In 2023, bluebird established a validated, commercial gene therapy strategy that brought ZYNTEGLO and SKYSONA to individuals living with beta-thalassemia and cerebral adrenoleukodystrophy. Building on that foundation, today we are positioned for robust commercial uptake of LYFGENIA for sickle cell disease, with a substantial QTC network in place, favorable Medicaid coverage being established, and demonstrated strong patient demand," said Andrew Obenshain, chief executive officer, bluebird bio. "Our recent agreement with Hercules Capital meaningfully extends our cash runway, and further enables us to capitalize on our commercial head start and bring our transformative gene therapies to patients and their families. In 2024, we anticipate between 85 to 105 patient starts across our three FDA approved therapies, laying the foundation for strong revenue growth."

RECENT COMPANY HIGHLIGHTS

Up to $175 million Debt Financing with Hercules Capital

On March 18, 2024, bluebird announced that it had entered into a five-year term loan facility with Hercules Capital. Under the terms of the agreement, the Company may draw up to $175 million, available in four tranches. The first tranche of $75 million was drawn at closing. The Company may draw upon two additional tranches of $25 million each, subject to satisfaction of certain conditions, including achievement of commercial milestones. The facility also provides for a fourth tranche of $50 million, available at the lender’s discretion.
Based on launch estimates and current business plans, and assuming three tranches totaling $125 million are executed, the transaction is projected to extend the Company’s cash runway through Q1 2026.
COMMERCIAL LAUNCH UPDATES

Strong patient uptake across portfolio

First LYFGENIA patient start imminent; multiple patients enrolled and preparing for treatment across QTC network.
Continued strong, linear growth for ZYNTEGLO with 7 patient starts since the beginning of 2024, in addition to 20 patient starts completed for ZYNTEGLO in 2023.
Completed 2 patient starts for SKYSONA since the beginning of 2024, in addition to 6 patient starts completed for SKYSONA in 2023.
Validated access and reimbursement strategy is driving favorable coverage landscape

In the first quarter of 2024, bluebird signed its first Medicaid outcomes-based agreement for LYFGENIA with the state of Michigan.
In addition to the Medicaid outcomes-based agreement, bluebird has signed four outcomes-based agreements for LYFGENIA with national commercial payer organizations and published coverage policies cover more than 200 million U.S. lives.
Discussions are ongoing with more than 15 Medicaid agencies representing 80% of Medicaid-insured individuals with sickle cell disease in the U.S. and the Company is engaged with the Center for Medicare and Medicaid Innovation (CMMI) on its Cell and Gene Therapy Access Model demonstration.
Timely access to ZYNTEGLO and SKYSONA has continued, with zero ultimate denials for either therapy across both Medicaid and commercial payers.
Substantial QTC footprint established

bluebird has activated 62 QTCs for ZYNTEGLO (defined as a signed MSA); capitalizing on launch synergies, 49 centers are already receiving referrals for LYFGENIA.
Five centers are also activated to administer SKYSONA for patients with cerebral adrenoleukodystrophy (CALD).
The Company anticipates continued QTC network expansion across its portfolio in 2024.
LOVO-CEL CLINICAL TRIAL UPDATE

Enrollment is ongoing for the HGB-210 study evaluating lovo-cel for patients under the age of 12. The Company anticipates enrollment to be complete in Q4 2024.
2024 GUIDANCE

The Company anticipates 85 to 105 patient starts (cell collections) combined across all three of its FDA approved therapies (LYFGENIA, ZYNTEGLO, SKYSONA) in 2024. Consistent with previous quarters, bluebird plans to provide quarterly updates on patient starts for each of its therapies.
Gross-to-net discounts across all three products are expected to be in the range of 20% to 25% of gross revenue in 2024 and will fluctuate based on product and payer mix, and well as utilization of outcomes-based agreements for LYFGENIA and ZYNTEGLO.
Based on projected timelines from cell collection to infusion, the Company expects to recognize revenue from its first infusion of LYFGENIA in the third quarter of 2024.
FOURTH QUARTER AND ANNUAL FINANCIAL HIGHLIGHTS

Cash Position: The Company’s cash, cash equivalents and restricted cash balance was approximately $275 million, including restricted cash of approximately $53 million, as of December 31, 2023.

Based on launch trajectory and current business plans, bluebird expects its cash and cash equivalents excluding restricted cash and assuming three tranches totaling $125 million in proceeds from its term loan facility are executed, will be sufficient to meet bluebird’s planned operating expenses and capital expenditure requirements through Q1 2026.

In the fourth quarter of 2023, the Company entered into a factoring agreement which is accelerating cash collection related to patient starts across its portfolio of approved therapies.
Revenue, net: Total revenue, net was $7.8 million for the three months ended December 31, 2023, compared to $0.1 million for the three months ended December 31, 2022.

Total revenue, net was $29.5 million for the twelve months ended December 31, 2023, compared to $3.6 million for the twelve months ended December 31, 2022. The increase of $25.9 million was primarily due to SKYSONA and ZYNTEGLO product revenue.

For the year ended December 31, 2023, product revenues by therapy represent $16.7 million attributable to ZYNTEGLO and $12.4 million attributable to SKYSONA, with gross-to-net discounts of approximately 19% across both products.
On March 26, 2024, bluebird announced that it will restate its consolidated financial statements for 2022, and for the first three quarters of both 2022 and 2023 in its Annual Report on Form 10-K for the year ended December 31, 2023 (the "2023 Form 10-K"). The restatements relate to the identification of embedded leases and the treatment of non-lease components contained in lease agreements with contract manufacturers. As a result, the Company anticipates recording an increase in lease assets and lease liabilities, as well as an increase in non-cash interest expense in each restated period. The Company does not expect the restatement to result in any impact on its cash position or revenue. bluebird anticipates filing its 2023 Form 10-K, inclusive of the restatement no later than April 16, 2024.

The financial results included in this press release represent the most current information available to the Company’s management. The Company expects that its actual results to be reported in its 2023 Form 10-K will not differ materially from the results included herein, however, these results are subject to change following the completion of the Company’s financial close procedures and the audit of its consolidated financial statements for the year ended December 31, 2023.

CONFERENCE CALL DETAILS

bluebird will hold a conference call to discuss its fourth quarter and 2023 annual results and business updates today, Tuesday, March 26, 2024, at 8:00 am ET.

To access the live conference call via telephone, please register at this link to receive a dial in number and unique PIN.

The live webcast of the call may be accessed by visiting the "Events & Presentations" page within the Investors & Media section of the bluebird website at View Source A replay of the webcast will be available on the bluebird website for 90 days following the event.