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.

On March 26, 2024 BioLineRx Ltd. (NASDAQ: BLRX) (TASE: BLRX), a commercial stage biopharmaceutical company pursuing life-changing therapies in oncology and rare diseases, reported its financial results for the year ended December 31, 2023, and provided recent corporate and portfolio updates (Press release, BioLineRx, MAR 26, 2024, https://ir.biolinerx.com/news-releases/news-release-details/biolinerx-reports-2023-financial-results-and-recent-corporate [SID1234641438]).

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"Following FDA approval of APHEXDA in September, physicians and transplant centers have been very receptive to the value of our strong clinical data, and our commercial team has made substantial progress establishing relationships with transplant centers across the country," said Philip Serlin, Chief Executive Officer of BioLineRx. "This year will continue to be primarily a foundational period for the commercialization of APHEXDA. We are seeing substantial progress on Pharmacy & Therapeutics committee approvals — the first step toward center adoption — and are actively supporting centers as they build usage protocols and treat their first patients. Initial feedback on patient experiences has been positive, and we are already seeing repeat purchases. Notably, we have achieved payer coverage representing approximately 95% of covered lives in the U.S. to date, which we believe reflects the value that APHEXDA offers to payers and patients alike, particularly its ability to mobilize the targeted number of stem cells in fewer apheresis sessions.

"Additionally, through a clinical collaboration with Washington University, we are actively evaluating the potential of motixafortide to support gene therapy for patients with sickle cell disease, a treatment process that requires significant quantities of hematopoietic stem cells. We anticipate data from this proof-of-concept Phase 1 study in patients with sickle cell disease in the second half of this year.

"At the same time, we are making significant progress advancing clinical programs evaluating motixafortide in pancreatic cancer, which if ultimately approved in combination with PD-1 inhibitors, would serve a much larger patient population and provide confidence for expanding into additional solid tumors. In pancreatic cancer, our enthusiasm is bolstered by the compelling data presented last fall from the single-arm pilot phase of the Phase 2b trial sponsored by Columbia University. The first patient has now been dosed in the randomized Phase 2b portion of that study, and we are also working with Gloria Biosciences on the design and execution of a similar randomized Phase 2b combination trial of motixafortide and zimberelimab in pancreatic cancer in China.

"Our vision of bringing a best-in-class stem cell mobilization agent to market, as well as advancing development in pancreatic cancer and other solid tumor areas with major unmet needs, is being actively realized. We look forward to the exciting, continued execution progress that our commercial and development teams will make this year," Mr. Serlin concluded.

Corporate Updates

Launched APHEXDA (motixafortide) in the U.S.
Announced closing of exclusive license agreement that includes development and commercialization rights to motixafortide across all indications in the Asia region, as well as a strategic equity investment
Strengthened motixafortide intellectual property estate with notice of allowance for U.S. patent covering method of manufacturing motixafortide suitable for large scale production; the patent supplements existing Orphan Drug Designation in the U.S. and Europe for the treatment of pancreatic cancer, as well as Orphan Drug market exclusivity for autologous stem cell mobilization in multiple myeloma patients in the U.S. following last year’s FDA approval of APHEXDA
APHEXDA Launch Updates

Reported positive coverage decisions by payers representing ~95% of all covered lives in the U.S.
Received inclusion of APHEXDA in the National Comprehensive Cancer Network (NCCN) guidelines for Hematopoietic Cell Transplantation
Achieved "on formulary" status for APHEXDA within targeted top 80 transplantation centers (which perform 85% of all U.S. transplants) managing ~20% of stem cell transplant procedures at these institutions; anticipate similar on formulary status of ~35% at end of Q2 2024 and ~60% at year-end 2024
Received Healthcare Common Procedure Coding System (HCPCS) J-Code to facilitate Medicare reimbursement for APHEXDA to transplant centers treating Medicare beneficiaries
Clinical Portfolio Updates

Motixafortide (selective inhibitor of CXCR4 chemokine receptor)

Multiple Myeloma

Presented posters at both the American Society of Hematology (ASH) (Free ASH Whitepaper) 65th Annual Meeting on December 10, 2023, and the 2024 Tandem Meetings on February 21-24, 2024. The posters reviewed combination premedication benefits in the Phase 3 GENESIS trial, extended PD effect of elevated CD34+ cells in peripheral blood, and a post-hoc subgroup analysis of impaired HSC mobilization patients that demonstrated a consistent benefit of motixafortide + G-CSF over placebo + G-CSF mobilization for all patients
Supported collaboration partner Gloria Biosciences with stem cell mobilization bridging study IND filing in February with the Center for Drug Evaluation of the National Medical Products Administration in China. Anticipate regulatory action in May 2024 and initiation of pivotal clinical trial in 2H 2024
Pancreatic Ductal Adenocarcinoma (mPDAC)

Announced first patient dosed in a randomized, investigator-initiated Phase 2b clinical trial in collaboration with Columbia University assessing motixafortide in combination with the PD-1 inhibitor cemiplimab and standard-of-care chemotherapy as first-line treatment in patients with metastatic pancreatic cancer
Advanced plans with collaboration partner Gloria Biosciences on a Phase 2b randomized clinical trial in China assessing motixafortide in combination with the PD-1 inhibitor zimberelimab and standard-of-care chemotherapy as first-line treatment in patients with metastatic pancreatic cancer. Anticipate clinical trial initiation in 2025
Sickle Cell Disease (SCD) & Gene Therapy

Continued to enroll patients into a clinical trial in collaboration with Washington University School of Medicine in St. Louis to evaluate motixafortide as monotherapy and in combination with natalizumab for stem cell mobilization for gene therapies in sickle cell disease. Anticipate data in 2H 2024
Financial Results for Year Ended December 31, 2023

Total revenues for the year ended December 31, 2023, were $4.8 million, compared to no revenues for the year ended December 31, 2022. Revenues in 2023 (all of which were recorded in the fourth quarter) primarily reflect a portion of the upfront payment from the Gloria Biosciences license agreement, of which $4.6 million was recognized in 2023, as well as $0.2 million of revenues from product sales of APHEXDA in the U.S.
Cost of revenues for the year ended December 31, 2023, amounted to $3.7 million, compared to no cost of revenues for the year ended December 31, 2022. The cost of revenues in 2023 (all of which was recorded in the fourth quarter) primarily reflects a $3.0 million sub-license fee to the upstream licensor of motixafortide payable on closing of the exclusive license agreement in Asia, as well as amortization of an intangible asset in respect of these license revenues in the amount of $0.5 million. Cost of product sales were insignificant, representing approximately 6% of related sales.
Research and development expenses for the year ended December 31, 2023, were $12.5 million, compared to $17.6 million for the year ended December 31, 2022. The decrease resulted primarily from lower expenses related to motixafortide NDA supporting activities, as well as lower expenses associated with completion of the AGI-134 study
Sales and marketing expenses for the year ended December 31, 2023, were $25.3 million, compared to $6.5 million for the year ended December 31, 2022. The increase resulted primarily from the ramp-up of pre-commercialization and commercialization activities related to motixafortide
General and administrative expenses for the year ended December 31, 2023, were $6.3 million, compared to $5.1 million for the year ended December 31, 2022. The increase resulted primarily from an increase in payroll and related expenses associated with a small headcount increase during the 2022 period, as well as an increase in professional services and legal expenses
Non-operating expenses for the year ended December 31, 2023, were $10.8 million, compared to non-operating income of $5.7 million for the year ended December 31, 2022. Non-operating expenses and income primarily relate to the non-cash revaluation of outstanding warrants resulting from changes in the company’s share price during the respective periods
Net loss for the year ended December 31, 2023 was $60.6 million, compared to $25.0 million for the year ended December 31, 2022. The net loss for 2023 included $17.8 million in non-cash expenses, specifically an expense of $11.1 million for the revaluation of warrants and a one-time $6.7 million impairment of intangible assets associated with discontinuation of the AGI-134 development program. The net loss for 2022 included $6.4 million in non-cash income specifically related to the revaluation of warrants.
As of December 31, 2023, the Company had cash, cash equivalents, and short-term bank deposits of $43.0 million. The Company anticipates that this amount and other available resources, including amounts available under a debt facility with Kreos Capital, will be sufficient to fund operations, as currently planned, into 2025
A copy of the Company’s annual report on Form 20-F for the year ended December 31, 2023 has been filed with the U.S. Securities and Exchange Commission at View Source and posted on the Company’s investor relations website at View Source Company will deliver a hard copy of its annual report, including its complete audited consolidated financial statements, free of charge, to its shareholders upon request at [email protected].

Conference Call and Webcast Information

To access the conference call, please dial +1-888-281-1167 from the U.S. or +972-3-918-0685 internationally. A live webcast and a replay of the call can be accessed through the event page on the Company’s website. Please allow extra time prior to the call to visit the site and download any necessary software to listen to the live broadcast. The call replay will be available approximately two hours after completion of the live conference call. A dial-in replay of the call will be available until March 28, 2024; please dial +1-888-295-2634 from the US or +972-3-925-5904 internationally.

On March 26, 2024 Ayala Pharmaceuticals, Inc. (OTCQX: ADXS), a clinical-stage oncology company, reported the completion of the previously announced sale of AL102, and related drug candidate AL101, to Immunome, Inc. (Nasdaq: IMNM) (Press release, Ayala Pharmaceuticals, MAR 26, 2024, View Source [SID1234641437]).

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As per the terms of the sale, Ayala received from Immunome $20 million in cash and 2,175,489 shares of Immunome common stock, and Immunome assumed specified liabilities related to AL102. Ayala may also receive up to an additional $37.5 million in development and commercial milestone payments.

"We are pleased that AL102 will now be advanced by the highly experienced team at Immunome," said Ken Berlin, President and CEO of Ayala Pharmaceuticals. "I am deeply grateful to the team at Ayala for the work they have done over the last several years to assemble compelling clinical data and reach this point."

A.G.P./Alliance Global Partners acted as strategic advisor to Ayala Pharmaceuticals, Inc. in connection with the transaction.