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Ascendis Presents Updated and New TransCon™ IL-2 ??? Monotherapy and Combination Therapy Data Confirming Clinical Activity Across Tumor Types at ESMO 2023

On October 26, 2023 Ascendis Pharma A/S (Nasdaq: ASND) reported updated and new data from its ongoing Phase 1/2 IL-Believe Trial of TransCon IL-2 β⁄γ in a poster presentation at ESMO (Free ESMO Whitepaper) 2023, the annual meeting of the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) held in Madrid, Spain (Press release, Ascendis Pharma, OCT 26, 2023, View Source [SID1234636362]). The data included longer-term follow up of previously presented TransCon IL-2 β⁄γ monotherapy data from the IL-Believe Trial, and was the first presentation of dose escalation data informing recommended Phase 2 dose (RP2D) for TransCon IL-2 β⁄γ in combination with a checkpoint inhibitor.

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As of the August 15, 2023 data cutoff, 46 patients were enrolled into dose escalation: 25 to monotherapy and 21 to combination therapy. Patients were heavily pretreated including some who previously progressed on checkpoint inhibitors. Anti-tumor clinical responses were observed with TransCon IL-2 β⁄γ both as monotherapy (colorectal cancer with confirmed partial response (PR)) and in combination with pembrolizumab (small cell lung cancer (SCLC), 1 with confirmed PR and, subsequent to the August 15, 2023 data cutoff, 1 ongoing with an unconfirmed complete response).

"These updated data reinforce the promising Phase 1 monotherapy data for TransCon IL-2 β⁄γ reported earlier this year, further strengthening our confidence in its best-in-class potential," said Stina Singel, M.D., Ph.D., Executive Vice President, Head of Clinical Development, Oncology at Ascendis Pharma. "In addition to previously reported monotherapy clinical activity, we are particularly encouraged to see anti-tumor responses in two of the three patients with SCLC in the combination portion of the trial who had previously progressed on checkpoint inhibitors. In the Phase 2 portion of IL-Believe, we continue enrolling into indication-specific cohorts and look forward to sharing preliminary data from these cohorts in the second half of 2024."

TransCon IL-2 β⁄γ is an investigational long-acting prodrug with sustained release of an IL-2Rβ⁄γ-selective analog (IL-2 β⁄γ) designed to address the known limitations of interleukin-2 (IL-2) cancer immunotherapy through prolonged activation of IL-2Rβ⁄γ with low Cmax. IL-Believe is investigating the safety and tolerability of TransCon IL-2 β⁄γ alone or in combination with the check-point inhibitor pembrolizumab and/or chemotherapy or TransCon TLR7/8 Agonist in participants with locally advanced or metastatic solid tumors. RP2D for IL-Believe is 120 µg/kg of TransCon IL-2 β⁄γ administered intravenously every three weeks in both the monotherapy and combination therapy arms.

Additional details and highlights from the ESMO (Free ESMO Whitepaper) poster are available on the Investor & News section of the Ascendis Pharma website at View Source

Alligator Bioscience AB reports financial results for the first 9 months of 2023 and for Q3 2023 and provides a business update

On October 26, 2023 Alligator Bioscience (Nasdaq Stockholm: ATORX) reported tis financial results for the third quarter ending September 30, 2023 (Press release, Alligator Bioscience, OCT 26, 2023, View Source [SID1234636361]).

"During another busy and productive quarter for Alligator we achieved one more important milestone in the clinical and commercial development of our lead asset with the addition of orphan designation for mitazalimab in pancreatic cancer by the European regulator. This follows our receipt of orphan drug designation in the US from the FDA and means we have now secured greater commercial protection for mitazalimab upon approval in our two key markets, the US and the EU. Over the summer, we showcased mitazalimab’s scientific achievements at several prestigious industry conferences, through which we continue to raise mitazalimab’s profile among the world’s top oncologists, investors and potential partners. On the partnership front, we reported the achievement of Technical Feasibility in one of our collaboration programs with Orion, which triggered a milestone payment to us. Our work with Orion is a great example of the benefits these strategic collaborations can deliver for our company and our shareholders. We have much to look forward to in the coming months, in particular the next major inflection point in our OPTIMIZE-1 study, which is due to report its top-line Phase 2 data at the start of next year and which will mark the start of the next stage of mitazalimab’s route to market."
Søren Bregenholt, CEO of Alligator Bioscience

BUSINESS UPDATE
Mitazalimab

On September 28-29, Alligator presented twice at the 2023 AACR (Free AACR Whitepaper) (American Association for Cancer Research) Special Conference on Pancreatic Cancer held in Boston. The first presentation was an oral presentation entitled "CD40 agonist mitazalimab in combination with mFOLFIRINOX in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC): Interim efficacy results of the OPTIMIZE phase 1b/2 study". The second was a poster presentation entitled "Interim pharmacodynamic analyses of mitazalimab in combination with FOLFIRINOX in first-line metastatic pancreatic ductal adenocarcinoma (mPDAC) identify CD4 effector T cells as a correlate of treatment outcomes".
On September 21, Alligator presented a poster at the 2023 International Cancer Immunotherapy Conference (CIMT) (Free CIMT Whitepaper) (CICON) held in Milan, entitled "Efficacy and pharmacodynamic biomarkers of mitazalimab in combination with chemotherapy in preclinical mouse models".
On August 21, Alligator announced that the European Medicines Agency had granted Orphan Designation to mitazalimab for the treatment of pancreatic cancer. The designation confers significant financial and regulatory benefits, including 10 years of marketing approval in the EU after product approval.
On July 19, Alligator presented an oral presentation at the 3rd Annual Tumor Myeloid-Directed Therapies Summit held in Boston entitled "Targeting CD40 on Myeloid Cells to Reverse the Suppressive Tumor Microenvironment & Enhance T Cell Priming".
Exercise of Warrants

On September 1, Alligator announced it would receive approximately SEK 13.8 million through the exercise of warrants of series TO 6, which represents an utilization rate of approximately 68 percent of the warrants attached to shares acquired through the preferential rights issue that took place in April 2023.
Milestone achieved in collaboration with Orion

On July 31, Alligator announced that Technical Feasibility had been achieved in the second program of the Company’s research collaboration and license agreement with Orion, triggering a new milestone payment to Alligator.
Significant events after the end of the period:

Mitazalimab

On October 11, the European Patent Office granted Alligator a new patent covering mitazalimab’s composition of matter until 2038, including a potential supplementary term. The patent expands protection for mitazalimab in Europe and brings the total number of patents in the mitazalimab intellectual property portfolio to 48 granted patents and 25 pending patents covering multiple territories, including Europe, North America, Asia and more.
ATOR-1017

On October 5, Alligator announced the publication of a peer-reviewed article entitled "ATOR-1017, an Fc-gamma receptor conditional 4-1BB agonist designed for optimal safety and efficacy, activates exhausted T cells in combination with anti-PD-1" in the journal Cancer Immunology, Immunotherapy.
FINANCIAL SUMMARY FOR Q3 2023 and YEAR-TO-DATE 2023
The financial summaries for the quarterly periods ending September 30th, 2023 and September 30th, 2022 are presented below.

All amounts in MSEK,
unless specified July – September 2023 July – September 2022
Net Sales 19.4 5.1
Operating profit/loss -52.7 -51.2
Profit/loss for the period -52.5 -51.4
Earnings per share (SEK)
before and after dilution -0.08 -0.23
Cash Flow -86.5 -45.6
Cash & Cash Equivalents including short-term financial assets 123.9 147.4

The financial summaries for the year-to-date periods ending September 30th, 2023 and September 30th, 2022 are presented below.

All amounts in MSEK,
unless specified January – September 2023 January – September 2022
Net Sales 46.4 15.6
Operating profit/loss -178.6 -140.1
Profit/loss for the period -178.8 -140.2
Earnings per share (SEK)
before and after dilution -0.45 -0.64
Cash Flow -23.1 -131.0
Cash & Cash Equivalents 123.9 147.4
The full report is attached as a PDF, and is also available on the company’s website via this link.

Alligator will host a conference call today at 12:30 p.m. CEST/ 6:30 a.m. ET for investors, analysts and media, where CEO Søren Bregenholt and CFO Marie Svensson will present and comment on the Q3 interim report, which will be followed by a Q&A session. The call will be held in English.

Results of Operations and Financial Condition

On October 26, 2023, 2seventy bio, Inc. (the "Company") reported that ABECMA (idecabtagene vicleucel, or ide-cel) generated approximately $69 million in U.S. revenue during the third quarter of 2023 (Press release, 2seventy bio, OCT 26, 2023, View Source [SID1234636360]). The Company and Bristol Myers Squibb ("BMS") share equally in all profits and losses related to development, manufacture and commercialization of ABECMA in the U.S. This announcement is based on information provided to the Company by BMS and is unaudited and does not present all information necessary for an understanding of the Company’s financial condition as of September 30, 2023 and its results of operations for the quarter then ended. The Company expects to announce its full results for the quarter ended September 30, 2023 on or before November 14, 2023. The Company also believes that the competitive dynamics impacting ABECMA will continue into the fourth quarter of 2023.

Circio presents powerful expression data for new generation circVec 2.0 design at the ESGCT 2023 annual meeting

On October 26, 2023 Circio reported the first generation circVec 1.0 genetic cassette based on "Nature´s best design" for human circRNA expression. Following rational, targeted optimization of specific sequences and regulatory elements, Circio has been able to further improve the circRNA biogenesis and translation rate, resulting in up to 10-fold increase in protein payload expression (Press release, Circio, OCT 26, 2023, View Source [SID1234636337]). To Circio´s knowledge, circVec 2.0 far exceeds any other known intra-cellular circRNA expression system, both in terms of circRNA biogenesis efficiency and protein yield.

Thomas Birkballe Hansen, VP and head of Research at Circio said: "We are continuing to evolve our circVec platform, and the enhanced 2.0 design drives potent and persistent protein expression. Durability and toxicity are major issues facing today´s gold-standard gene therapy approaches, which we believe can be overcome by switching from current mRNA-based expression to our circVec system. We have not reached the full potential of our technology yet, and we are continuously exploring further optimization strategies towards circVec 3.0 and beyond."

The data presented at ESGCT 2023 demonstrates the importance of optimizing both the DNA genetic cassette and the circRNA design to maximize protein payload expression. By modifying the flanking inverted repeat elements (IR), circRNA biogenesis was improved by 2-3 -fold vs. circVec 1.0. Screening and selecting novel internal ribosome entry site (IRES) elements increased the protein translation rate by 2-6 -fold. Combining these modifications, the resulting protein payload expression was enhanced by 3-10-fold vs. circVec 1.0 (depending on cell type), and outcompeted mRNA already at early time points.

Furthermore, bioinformatic modelling of long-term dynamics, based on Circio´s experimental results and externally published data, showed substantially elevated and more durable expression levels from circRNA compared to conventional mRNA vectors. This characteristic can enable improved therapeutic potency, lower dosing, and reduced toxicity. As such, circRNA is expected to replace mRNA as the preferred expression system for all viral and DNA-based therapeutics in the future.

Please see the poster here: 2023 ESGCT poster

SparX Biopharmaceutical Announces IND Submission to the FDA for Its SPX-303, A First-In-Human anti-LILRB2/PD-L1 Antibody Drug

On October 25, 2023 SparX Biopharmaceutical reported its Investigational New Drug (IND) submission to the U.S. Food and Drug Administration (FDA) for SPX-303, a First-in-Class anti-LILRB2/PD-L1 bispecific antibody drug candidate. This monumental step underscores SparX’s steadfast commitment to unveiling groundbreaking solutions for patients grappling with advanced or refractory solid tumors.

Dr. Gui-Dong Zhu, Chief Executive Officer of SparX Biopharmaceutical, expressed his enthusiasm: "This IND submission marks a crucial juncture in our determined pursuit to revolutionize cancer treatment. The initial data for SPX-303 is not only promising but fortifies our resolve to materialize its therapeutic potential in a clinical milieu, especially for those patients constrained by limited treatment avenues."

Upon the greenlight from the agency, SparX Biopharmaceutical is poised to commence a Phase 1 clinical study, evaluating the safety, tolerability, and preliminary efficacy of SPX-303 in patients beleaguered by advanced or refractory solid tumors. This inaugural human trial stands as a critical endeavor in assessing the unprecedented therapeutic capacities of SPX-303, setting an era of innovative and enhanced healthcare solutions..

Developed by SparX, SPX-303 emerges as a novel bispecific antibody therapy, designed to concurrently engage two fundamental immune checkpoint proteins, LILRB2 and PD-L1. Both proteins are quintessential regulators in upholding the immune system’s homeostasis and robustness, forestalling autoimmune malfunctions. LILRB2 predominantly mitigates excessive innate immune responses, preserving the body’s inherent defensive balance, while PD-L1, frequently amplified in tumor cells, judiciously regulates T cell activation, ensuring a precise and restrained immune response. Cancer, with its deceptive mechanisms, often exploits these checkpoints, thereby gaining a defensive shield against immune attacks and proliferating unrestrained. SPX-303 is meticulously crafted to breach this shield, enabling the immune system to identify and robustly obliterate malignant cells, marking a new epoch in cancer therapy.

(Press release, Sparx Therapeutics, OCT 25, 2023, View Source [SID1234661037])