On November 14, 2024 Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or "the Company"), a clinical-stage biotechnology company developing novel LAG-3 immunotherapiesfor cancer and autoimmune disease, reported the presentation of new data from EFTISARC-NEO, a Phase II investigator-initiated trial of eftilagimod alpha (efti) in combination with radiotherapy plus KEYTRUDA (pembrolizumab) for patients with soft tissue sarcoma (STS), at the Connective Tissue Oncology Society (CTOS) 2024 Annual Meeting (Press release, Immutep, NOV 14, 2024, View Source [SID1234648305]). Based on preliminary analysis among 21 patients available for primary endpoint assessment, the triple combination therapy demonstrates significant efficacy in the neoadjuvant setting for resectable STS.

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Katarzyna Kozak, M.D., Ph.D., and Paweł Sobczuk, M.D., Ph.D., medical oncologists at the Department of Soft Tissue/Bone Sarcoma and Melanoma at MSCNRIO (Warsaw) and the trial’s principal investigators, stated: "Our belief in efti’s unique mechanism of action to complement radiotherapy and pembrolizumab in order drive better outcomes for patients with this rare aggressive disease was the foundation of the EFTISARC-NEO trial. These very encouraging results we are presenting today build our confidence in the synergistic effects of this new therapeutic approach and its potential to treat these patients in dire need of more effective therapies. In particular, the high level of hyalinization/fibrosis achieved with this novel combination therapy, three-times above historical results from standard radiotherapy, demonstrates remarkable efficacy in patients with resectable soft tissue sarcomas."

In the neoadjuvant setting for patients with resectable STS, the combination achieved a greater than threefold increase in tumour hyalinization/fibrosis (median 50%) at the time of surgical resection as compared to a historical median 15% from standard radiotherapy alone. In addition to being the primary endpoint of the EFTISARC-NEO study, the tumour hyalinization/fibrosisrate has also been identified as an important predictor of overall survival for STS patients.

The EFTISARC-NEO trial, with a data cut-off of 20 October 2024, also showed 71.4% of patients achieved a pathologic response defined as ≥35% of hyalinization/fibrosis and 9.5% of patients achieved a complete pathologic response. The triple combination therapy is safe with no grade ≥3 toxicities related to efti and pembrolizumab.

Dr. Frédéric Triebel, CSO of Immutep, said: "We are pleased with the strength of these preliminary results in this difficult-to-treat cancer. To see 71.4% of soft tissue sarcoma patients achieving a pathologic response defined as ≥35% of hyalinization/fibrosis combined with low viable tumour cells at 8% is very promising, especially as strong efficacy has been observed in different STS subtypes. We look forward to further evaluation of efti’s potential as neoadjuvant immunotherapy to help drive improved clinical outcomes.

The ongoing open-label EFTISARC-NEO Phase II study, conducted by the Maria Skłodowska-Curie National Research Institute of Oncology (MSCNRIO) in Warsaw, is expected to reach the planned enrolment of 40 patients in Q1 CY2025. The trial is primarily funded with an approved grant from the Polish government awarded by the Polish Medical Research Agency program. For more information, visit clinicaltrials.gov (NCT06128863)

On November 14, 2024 bluebird bio, Inc. (NASDAQ: BLUE) ("bluebird bio" or the "Company") reported third quarter results and business highlights for the quarter ended September 30, 2024, including recent commercial and operational progress (Press release, bluebird bio, NOV 14, 2024, View Source [SID1234648391]).

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"Patient starts more than doubled from our second to third quarter update, providing clear evidence that our commercial launches continued to accelerate," said Andrew Obenshain, chief executive officer. "This momentum, coupled with steps we took in the third quarter to increase manufacturing capacity for ZYNTEGLO and optimize our cost structure, is propelling bluebird forward on our path to becoming a sustainable commercial gene therapy company. We remain focused on securing additional cash resources to extend our runway, which we believe would enable us to achieve this vision and reach cash flow break-even in the second half of 2025."

COMMERCIAL LAUNCH UPDATES

Continued commercial momentum across the portfolio

57 patient starts completed to date in 2024 (35 ZYNTEGLO, 17 LYFGENIA, 5 SKYSONA).
17 additional starts scheduled through the remainder of 2024.
Evidence of strong commercial demand, with 30 patient starts already scheduled in 2025, supporting the potential for cash flow breakeven in the second half of 2025.
More than 70 activated QTCs, with 40% having initiated or completed treatment for at least one patient.
Validated access and reimbursement strategy is driving favorable coverage landscape

To date, more than half of all states have affirmed coverage for LYFGENIA through a preferred drug list or published coverage criteria.
Nearly 50% of Medicaid-insured individuals with sickle cell disease in the U.S. live in a state that has already completed prior authorization approval for the use of LYFGENIA for at least one patient.
Multiple outcomes-based agreements are published and in place for LYFGENIA with national commercial payer organizations, representing more than 200 million U.S. lives.
DATA PRESENTATIONS AT ASH (Free ASH Whitepaper) 2024

Updated data from the Company’s lentiviral vector (LVV) gene addition programs in patients with sickle cell disease who have a history of vaso-occlusive events and patients with beta-thalassemia who require regular blood transfusions will be presented at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition. The meeting will take place December 7-10, 2024 at the San Diego Convention Center and online.

SICKLE CELL DISEASE DATA

Oral Presentation [#511]: An Update on Lovotibeglogene Autotemcel (lovo-cel) Clinical Trials for Sickle Cell Disease (SCD) and Analysis of Early Predictors of Response to Lovo-cel
Presenting Author: Dr. Stacey Rifkin-Zenenberg (Hackensack)
Date/Time: Sunday, December 8, 2024, 9:30 a.m. – 11:00 a.m. PT
Poster Presentation [#3576]: Participants with a History of Stroke in Lovotibeglogene Autotemcel (lovo-cel) Clinical Trials
Presenting Author: Dr. Jen Jaroscak (The Medical University of South Carolina)
Date/Time: Sunday, December 8, 2024, 6:00 p.m. – 8:00 p.m. PT
BETA-THALASSEMIA DATA

Poster Presentation [#2194]: Betibeglogene Autotemcel (beti-cel) Gene Addition Therapy results in durable Hemoglobin A (HbA) Production with up to 10 Years of Follow-Up in Participants with Transfusion-Dependent β-Thalassemia
Presenting Author: Dr. Alexis A Thompson (Children’s Hospital of Philadelphia)
Date/Time: Saturday, December 7, 2024, 5:30 p.m. – 7:30 p.m. PT
Abstracts outlining bluebird bio’s accepted data at ASH (Free ASH Whitepaper) 2024 are available on the ASH (Free ASH Whitepaper) conference website.

THIRD QUARTER FINANCIAL HIGHLIGHTS

Cash Position: The Company’s cash, cash equivalents and restricted cash balance was approximately $118.7 million, including restricted cash of approximately $48.0 million, as of September 30, 2024.

bluebird and Hercules are engaging collaboratively as bluebird works to secure adequate cash runway to obtain additional financing and reach cash flow break-even. Based on current forecasts, which assume continued cost-saving initiatives, successfully renegotiating key contracts, and continued collaborative engagement from Hercules, we expect our existing cash and cash equivalents will enable us to fund our operations into the first quarter of 2025.

The Company anticipates quarterly cash flow break-even in the second half of 2025, assuming it scales to approximately 40 drug product deliveries per quarter and obtains additional cash resources to extend its runway.
Revenue, net: Total revenue, net was $10.6 million for the three months ended September 30, 2024, compared to $12.3 million for the three months ended September 30, 2023, driven by quarter-to-quarter variability in drug product infusions.

Revenue for the third quarter includes revenue from LYFGENIA, following the completion of the first infusion for sickle cell disease.

bluebird previously guided to an anticipated reduction of net revenue in the third quarter; the Company now anticipates net revenue of at least $25 million in the fourth quarter 2024, as previously reported patient starts are infused.
Cost of Product Revenue: Cost of product revenue was $11.8 million for the three months ended September 30, 2024, compared to $9.1 million for the three months ended September 30, 2023.
SG&A Expenses: Selling, general and administrative expenses were $39.8 million for the three months ended September 30, 2024, compared to $40.8 million for the three months ended September 30, 2023. The decrease of $1.0 million was primarily driven by decrease in employee compensation, benefit, and other headcount related expenses, commercial expenses, and facility fees, partially offset by increased professional services fees.
R&D Expenses: Research and development expenses were $23.2 million for the three months ended September 30, 2024, compared to $58.5 million for the three months ended September 30, 2023. The decrease of $35.3 million was primarily driven by material production shift to inventory and cost of product revenue as well as decreased employee compensation, benefit, and other headcount related expenses, consulting fees, and facility and information technology fees.
Net income (loss): Net loss was $60.8 million for the three months ended September 30, 2024, compared to a net loss of $87.2 million for the three months ended September 30, 2023.
CONFERENCE CALL DETAILS

bluebird will hold a conference call to discuss its third quarter 2024 results and business updates today, Wednesday, November 14, 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.

To access the live webcast, please visit the "Events & Presentations" page within the Investors & Media section of the bluebird bio website at View Source A replay of the webcast will be available on the bluebird bio website for 90 days following the event.

On November 14, 2024 Moleculin Biotech, Inc., (Nasdaq: MBRX) ("Moleculin" or the "Company"), a late-stage pharmaceutical company with a broad portfolio of drug candidates targeting hard-to-treat tumors and viruses, reported it has amended the clinical trial protocol with the U.S. Food and Drug Administration ("FDA") for its Phase 3 pivotal trial protocol evaluating Annamycin in combination with Cytarabine (also known as "Ara-C" and for which the combination of Annamycin and Ara-C is referred to as "AnnAraC") for the treatment of AML patients who are refractory to or relapsed after induction therapy (R/R AML) (MB-108) (Press release, Moleculin, NOV 14, 2024, View Source [SID1234648407]). This Phase 3 "MIRACLE" trial (derived from Moleculin R/R AML AnnAraC Clinical Evaluation) will be a global trial, including sites in the US. Additionally, the Company released a Virtual Investor "What This Means" segment to discuss the amended protocol. Access the segment here.

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"Our team has been thoughtful and strategic with the design of the MIRACLE trial, which may allow for possible accelerated approval of Annamycin in combination with cytarabine for the treatment of relapsed or refractory AML. This amended protocol enables us to share definitive data earlier, which helps to partially de-risk financing the trial and potentially accelerates the timeline for strategic partnering. We believe that the unblinding of data at 45 subjects will enable us to begin assessing all three arms of the study and provide us with a clear path forward in understanding the potential of Annamycin for AML patients. This change now puts us potentially less than 12 months away from definitive unblinded data that could be a strong indicator of our likelihood of approval, and the kind of data that is likely to drive advanced partnering discussions," commented Walter Klemp, Chairman and Chief Executive Officer of Moleculin.

The MIRACLE study, subject to appropriate future filings with and potential additional feedback from the FDA and their foreign equivalents, is expected to initially utilize an adaptive design whereby the first 75 to 90 subjects will be randomized in Part A of the trial to receive high dose cytarabine (HiDAC) combined with either placebo, 190 mg/m2 of Annamycin, or 230 mg/m2 of Annamycin, such doses were specifically recommended by the FDA in the Company’s end of Phase 1B/2 meeting. The amended protocol will allow for the unblinding of preliminary primary efficacy data (CR) and safety/tolerability of the three arms at 45 subjects. This early unblinding will yield 30 subjects with Annamycin (190mg/m2 and 230/m2) and HiDAC and 15 subjects with just HiDAC. The Company expects to reach 45 subjects in the second half of 2025, in addition to the planned unblinding expected in 2026 of the next 30-45 subjects.

For Part B of the trial, approximately 244 additional subjects will be randomized to receive either HiDAC plus placebo or HiDAC plus the optimum dose of Annamycin. The selection of the optimum dose will be based on the overall balance of safety, pharmacokinetics and efficacy, consistent with the FDA’s new Project Optimus initiative. This increase from 240 to 244 subjects represents the statistical "cost" of the additional unblinding.

The amended protocol is currently being reviewed by the Institutional Review Board (IRB). Once approved, the amended protocol will be filed with the amendment for the Company’s Initial New Drug (IND) application in the US with the FDA.

Annamycin currently has Fast Track Status and Orphan Drug Designation from the FDA for the treatment of relapsed or refractory acute myeloid leukemia, in addition to Orphan Drug Designation for the treatment of soft tissue sarcoma. Furthermore, Annamycin has Orphan Drug Designation for the treatment of relapsed or refractory acute myeloid leukemia from the European Medicines Agency (EMA).

On November 14, 2024 GordonMD Global Investments LP reported that its portfolio company, Flare Therapeutics Inc., has entered into a strategic discovery collaboration with Roche (SIX: RO, ROG; OTCQX: RHHBY). Flare will lead discovery and preclinical activities targeting multiple transcription factor targets in oncology, while Roche will pursue the further preclinical and clinical development and commercialization of potential products from the collaboration, leveraging its industry-leading capabilities in oncology (Press release, Flare Therapeutics, NOV 14, 2024, View Source [SID1234648424]).

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Combining Flare’s advanced proteomic and mass spectrometry platform — powered by its proprietary library of electrophilic compounds — to discover small molecule drugs targeting transcription factors previously deemed yet to be affected by drugs in oncology with Roche’s experience in developing and manufacturing medicines, this collaboration seeks to advance potentially transformative therapies for patients living with cancer.

Flare will receive a US$70 million upfront cash payment and is eligible to receive discovery, development, and commercialization milestone payments potentially exceeding US$1.8 billion and royalties. Additionally, Flare retains a right to co-fund development for one target under the collaboration in exchange for increased royalties in the United States for this target. Flare will retain ownership of its existing pipeline, including its lead clinical-stage program, FX-909, in advanced urothelial cancer, its prostate cancer program entering IND-enabling studies, and other programs in discovery and early development in oncology and other therapeutic areas.

"This collaboration reinforces Flare’s capacity to advance its breakthrough science," said Dr. Craig Gordon, Chief Executive Officer of GordonMD.

"We look forward to our partnership with Roche because we share a commitment to tackling the most challenging disease areas with novel approaches and overcoming the difficulties of drugging transcription factors," said Rob Sims, Ph.D., Chief Scientific Officer and Co-founder of Flare Therapeutics.

On November 14, 2024 Candel Therapeutics, Inc. (Candel or the Company) (Nasdaq: CADL), a clinical stage biopharmaceutical company focused on developing multimodal biological immunotherapies to help patients fight cancer, reported financial results for the third quarter ended September 30, 2024, and provided a corporate update (Press release, Candel Therapeutics, NOV 14, 2024, View Source [SID1234648392]).

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"We remain on track for phase 2b and phase 3 topline data in non-metastatic, localized prostate cancer for CAN-2409 in the fourth quarter of 2024, and hope we will deliver the data and regulatory approvals to enable a paradigm shift in how these patients will be treated in the future. We continue to advance our clinical and pre-clinical candidates, while leveraging our robust enLIGHTENTM Discovery Platform to identify new and innovative assets that may be impactful in cancer immunotherapy," said Paul Peter Tak, MD, PhD, FMedSci, President and Chief Executive Officer of Candel. "We are encouraged by the first clinical and biomarker activity data after repeated injection of CAN-3110 from our ongoing phase 1b clinical trial of CAN-3110 in recurrent high-grade glioma, which suggests a long tail of survival. We are also excited about the data that supports potential expansion of CAN-3110 from recurrent high-grade glioma into melanoma, where we observed antitumor activity in pre-clinical models."

Dr. Tak continued, "As to the future, we are also looking forward to reporting updated overall survival data from both our ongoing CAN-2409 phase 2 NSCLC and pancreatic cancer clinical trials in Q1 2025."

Third Quarter 2024 & Recent Highlights

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CAN-3110 – Recurrent High-Grade Glioma
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Received orphan drug designation from the U.S. Food and Drug Administration (FDA) for CAN-3110 for the treatment of recurrent high-grade glioma (rHGG).
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Presented a Trial-in-Progress poster at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting on the ongoing phase 1b clinical trial exploring multiple doses of CAN-3110 in patients with rHGG.
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Presented clinical and biomarker activity data from the ongoing phase 1b clinical trial at the 16th Annual International Oncolytic Virotherapy Conference (IOVC).
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In the oral presentation, the investigators reported ongoing improved survival compared to historical controls, with 3 out of 6 patients still alive after more than one year (12.2, 13.0, and 18.7 months, respectively) after initiation of experimental treatment with repeated CAN-3110 injections.
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The data also show discrepancies between imaging and histologic findings, suggesting radiologic pseudo-progression: there was a near absence of tumor cells alongside dense lymphocyte infiltrates in biopsies obtained after CAN-3110 administration, especially in patients with enhancement on post-treatment magnetic resonance imaging (MRI) scans.
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CAN-3110 – Melanoma
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Presented preclinical results on the therapeutic potential of CAN-3110 in the Ras-Raf pathway altered melanoma model at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s 39th Annual Meeting.
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CAN-3110 exhibited potent, tumor-specific cytotoxicity in human and murine melanoma cell lines with varied CDKN2A pathway alterations and Nestin expression. In vivo mouse studies showed dose-dependent inhibition of tumor growth, with regression observed in a subset (3 of 8) of tumors treated with a high dose of CAN-3110.

▪
Cytotoxic activity in melanoma-bearing mice was associated with systemic immune activation, including increased activation and proliferation of circulating T cells.
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Findings mirror those from rHGG patients treated with CAN-3110 reported last year in Nature. The therapy was well-tolerated in preclinical models based on body weight and histopathological analysis following intratumoral administration.
o
enLIGHTEN Discovery Platform
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Presented poster titled "A first-in-class multimodal immunotherapy for enhanced immune activation in the tumor microenvironment as a novel therapeutic strategy for solid tumors" at IOVC.
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The presentation focused on the latest asset from the enLIGHTEN Discovery Platform, a multimodal viral therapeutic candidate encoding IL-12 and IL-15. Data showed the ability of the asset to induce expansion and activation of natural killer and CD8+ T cell populations, resulting in significant tumor growth inhibition and regression in two different models.
Anticipated Milestones

•
Phase 2b topline data for CAN-2409 in low-to-intermediate-risk, localized, non-metastatic prostate cancer expected in Q4 2024.
•
Phase 3 topline disease-free survival data for CAN-2409 in localized intermediate/high-risk prostate cancer expected in Q4 2024.
Financial Results for Third Quarter Ended September 30, 2024

Research and Development Expenses: Research and development expenses were $5.4 million for the third quarter of 2024 compared to $5.8 million for the third quarter of 2023. The decrease was primarily due to lower payroll-related expenses following the corporate restructuring in the fourth quarter of 2023 and a decrease in depreciation, impairment, and loss on the sale of fixed assets. These decreases were partially offset by clinical development costs driven by increased manufacturing costs for CAN-2409 programs. Research and development expenses included non-cash stock compensation expense of $0.6 million for the third quarter of 2024 compared to $0.3 million for the third quarter of 2023.

General and Administrative Expenses: General and administrative expenses were $3.3 million for the third quarter of 2024 compared to $3.0 million for the third quarter of 2023. The increase was primarily due to increased professional and consulting fees. The increase was partially offset by lower insurance costs. General and administrative expenses included non-cash stock compensation expense of $0.5 million for the third quarter of 2024 compared to $0.4 million for the third quarter of 2023.

Net Loss: Net loss for the third quarter of 2024 was $10.6 million, compared to a net loss of $8.4 million for the third quarter of 2023, and included other expense, net of $1.9 million for the third quarter of 2024 and other income, net of $0.4 million for the third quarter of 2023, primarily due to the change in the fair value of the Company’s warrant liability.

Cash Position: Cash and cash equivalents, as of September 30, 2024, were $16.6 million, as compared to $35.4 million as of December 31, 2023. Based on current plans and assumptions, the Company expects that its existing cash and cash equivalents will be sufficient to fund its current operating plan to the end of the first quarter of 2025.