On October 4, 2024 Molecular Partners AG (SIX: MOLN; NASDAQ: MOLN), a clinical-stage biotech company developing a new class of custom-built protein drugs known as DARPin therapeutics, reported that the Company will introduce proof-of-concept data for its new CD3 Switch-DARPin designed to overcome current T cell engager challenges in solid tumors, as well as present additional analyses from its Phase 1 study of MP0317 in patients with advanced solid tumors, at the 2024 Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), being held November 8-10 in Houston, TX (Press release, Molecular Partners, OCT 4, 2024, View Source [SID1234647017]).

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The poster presentation details are as follows:

Title: Unlocking precision: a next generation multi-specific CD3 Switch-DARPin with enhanced function to tackle the current limitations of T cell engagers in ovarian cancer
Abstract & Poster Number: 842

Title: Comprehensive biomarker analyses from a Phase 1 study reveals marked tumor microenvironment modulation in patients with advanced solid tumors treated with MP0317, a FAP-localized CD40 agonistic DARPin
Abstract & Poster Number: 612

Timing & Location: November 9, 2024 at 9 am – 8:30 pm CT; Exhibit Halls AB

The posters will be made available on Molecular Partners’ website after the conference.

On October 4, 2024 Onchilles Pharma, a private biotech company developing pan-cancer therapeutics that leverage the ELANE pathway, a novel innate immune mechanism of action for potent and selective cancer killing, reported that it will present new preclinical data for its NEU-002 program for systemic delivery at the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) (Press release, Onchilles Pharma, OCT 4, 2024, View Source [SID1234647034]). The meeting will be held both virtually and at the George R. Brown Convention Center in Houston from November 8-10, 2024.

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Presentation Details

Poster Title: NEU-002 leverages a cancer-specific innate immune pathway to induce immunogenic cell death and stimulate anti-tumor immunity

Abstract Number: 1297

Date and Time: Friday, November 8, 2024, 9:00 a.m. to 7:00 p.m. CST

Location: George R. Brown Convention Center, Level 1, Exhibit Halls AB or at View Source

About the NEU-002 Program and the ELANE Pathway

Onchilles’ scientific founder, Dr. Lev Becker, discovered that human neutrophils release neutrophil elastase (ELANE), which selectively and potently kills cancer cells while sparing healthy cells. This novel innate mechanism of action, known as the ELANE pathway, was published in the journal Cell in 2021. Targeting the ELANE pathway enables the eradication of cancer cells regardless of their genetic makeup, anatomical origin, or immune status. Building on these findings, Onchilles has developed NEU-001 (N17350) for intratumoral delivery and NEU-002 for intravenous delivery and has generated an extensive preclinical dataset showing strong monotherapy efficacy across many tumor types. This efficacy is mediated by immunogenic cancer cell death and mobilization of the immune system, leading to durable responses in preclinical mouse models.

On October 4, 2024 ABL Bio (CEO Sang Hoon Lee), a company specializing in bispecific antibodies, reported that it has entered into a clinical trial collaboration and supply agreement with MSD (a subsidiary of Merck & Co., Inc., Rahway, NJ, USA), to evaluate ABL103 in combination with MSD’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab) in patients with advanced or metastatic solid tumors (Press release, ABL Bio, OCT 4, 2024, View Source [SID1234647018]).

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Under the terms of the agreement, ABL Bio will conduct a phase 1b/2 clinical trial to evaluate the safety and efficacy of ABL103 in combination with KEYTRUDA. In this combination study, MSD will supply KEYTRUDA.

ABL103 is bispecific antibody that simultaneously targets B7-H4 and 4-1BB. ABL103 is one of the pipeline programs in which ABL Bio’s 4-1BB based bispecific antibody platform ‘Grabody-T’ has been applied. Grabody-T is designed to activate T cells only in the tumor microenvironment, reducing the liver toxicity of conventional 4-1BB monoclonal antibody and enhancing the antitumor activity.

ABL103 also has mechanism to activate the 4-1BB signaling pathways in the tumor microenvironments where the B7-H4 antigens exist, allowing T cells to selectively attack tumor cells while sparing normal cells. Currently, the dose escalation part of the phase 1 clinical trial for ABL103 is ongoing in South Korea.

Sang Hoon Lee, CEO of ABL Bio said "we are pleased to enter into this clinical collaboration agreement with MSD. With this agreement, we are ready to move on to the next stage of ABL103 clinical development. We hope that the combination of ABL103 and KEYTRUDA contributes to a better life for patients with advanced or metastatic solid tumors. To date, the phase 1 study for ABL103 monotherapy is progressing smoothly, and we will do our best in clinical development to achieve meaningful results from ABL103."

Meanwhile, ABL Bio is developing various clinical and non-clinical assets based on its bispecific antibody platform ‘Grabody’. More than 15 clinical projects for more than 7 assets, including ABL001, ABL111, ABL503, ABL105, ABL202, ABL301, and ABL103, are underway for different indications in various countries, including the United States, China, Australia, and Korea. In the case of ABL001, the U.S. Food and Drug Administration (FDA) recently granted Fast Track designation to support the rapid development of this new drug candidate. Meanwhile, ABL Bio is preparing to initiate clinical trials for ABL104. In addition, ABL Bio is continuously researching and developing several other product candidates, including bispecific antibody-drug conjugates (ADCs).

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

On October 4, 2024 Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC), a leading clinical-stage company specializing in immunotherapy for oncology, reported a corporate update to provide investors with a deeper understanding of recent data and what is expected for 2025 (Press release, Oncolytics Biotech, OCT 4, 2024, View Source [SID1234647035]).

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"We’re excited by the recent BRACELET-1 results, which exceeded our expectations and substantiate the strong efficacy signal previously observed in breast cancer patients treated with pelareorep," said Wayne Pisano, Interim CEO and Chair of Oncolytics’ Board of Directors. "Having treated well over 100 HR+/HER2- metastatic breast cancer patients in multiple clinical studies, these results provide the basis for a development path leading to an accelerated approval. The BRACELET-1 results, combined with recent feedback from the FDA, give us confidence in our development approach, and we look forward to initiating a clinical trial designed to support the approval of pelareorep as a novel breast cancer therapeutic."

Mr. Pisano continued, "The gastrointestinal cancer data also supports making pancreatic cancer a major priority for the company. To advance this development, we’ve established a collaboration with the Global Coalition for Adaptive Research (GCAR), and The Pancreatic Cancer Action Network (PanCAN) has provided us with the funding to further investigate pelareorep in pancreatic cancer through our GOBLET study. Having demonstrated pelareorep’s efficacy across multiple cancer indications and with important data readouts and future studies on the horizon, I’m looking forward to these next few years of Oncolytics’ growth and development."

Planned HR+/HER2- metastatic breast cancer study could open the door to an accelerated approval

The strong efficacy results from BRACELET-1 provide the foundation for a large Phase 2 study designed to support an accelerated approval. Early in 2025, we plan to submit to the FDA a pelareorep + paclitaxel combination therapy breast cancer trial. The study will enroll approximately 180 patients with HR+/HER2- advanced/metastatic breast cancer who have progressed on antibody-drug conjugates (ADCs) like Enhertu, who are not eligible for ADCs, or who cannot tolerate ADCs, which represents a patient population of approximately 55,000 patients in the US.1-4 The study design has sufficient statistical power to deliver a p-value of < 0.05 with a progression-free survival (PFS) benefit of ≥4.3 months. Notably, the BRACELET-1 study demonstrated a 5.7-month PFS benefit for the pelareorep + paclitaxel arm compared to chemotherapy alone, as detailed below. Enrollment in the registration-enabling study is expected to commence in the first half of 2025.

Thomas Heineman, M.D., Ph.D., Chief Medical Officer at Oncolytics, commented, "With the continuing evolution of breast cancer treatment, we have designed our breast cancer program with the guidance of leading experts in the field. Our first randomized study in breast cancer, IND-213, demonstrated the ability of pelareorep combination therapy to improve survival in heavily pre-treated patients with advanced or metastatic HR+/HER2- disease. The subsequent randomized BRACELET-1 study showed that pelareorep combination therapy could improve outcomes in HR+/HER2- breast cancer patients who had received prior CDK4/6 inhibitors. Based on the success of these studies, we are now ready to pursue a large phase 2 study powered to support an accelerated approval in the setting of ADC therapies such as Enhertu. Our plan is designed to obtain a regulatory approval with fewer patients, in a shorter time, and requiring less funding than traditional regulatory pathways. Our thorough understanding of pelareorep’s mechanism of action makes us confident that pelareorep-based combination therapy will continue to deliver strong clinical benefits to HR+/HER2- breast cancer patients within the current treatment approach."

BRACELET-1 efficacy data in HR+/HER2- metastatic breast cancer

The recently reported final BRACELET-1 study results provide clear evidence of pelareorep’s ability to improve outcomes in patients with advanced breast cancer (link to press release). Patients in the paclitaxel control arm had a median overall survival of 18.2 months. However, more than half of the patients in the pelareorep combination therapy arm were still alive at the time of the final survival analysis, resulting in a median overall survival of "Not Reached." A conservative estimate of median overall survival for the pelareorep arm is 32.1 months, demonstrating that pelareorep + paclitaxel delivered a greater than 12-month survival advantage compared to paclitaxel alone. This survival benefit is further illustrated by the 24-month overall survival rate, which showed that 64% of patients treated with pelareorep combination therapy survived at least 2 years compared to only 33% of patients treated with paclitaxel alone. In addition, final progression-free survival was 12.1 months for pelareorep + paclitaxel compared to 6.4 months for paclitaxel alone, yielding a benefit of 5.7 months.

Gastrointestinal cancer opportunities

We also anticipate continuing our development of pelareorep in gastrointestinal cancers. Once the master protocol has been finalized with GCAR for the pelareorep combination therapy, we intend to approach the FDA before the end of the year. This study is designed to produce registrational data. Additionally, we continue to evaluate pelareorep combination therapy in patients with anal cancer, building on the promising initial efficacy data in this patient population. If the expanded results continue to show a favorable efficacy signal, we anticipate moving directly to a registration-enabling study. Finally, we expect to provide updates on cohort 5 of the GOBLET study, which is investigating pelareorep in pancreatic cancer in combination with the chemotherapy modified FOLFIRINOX (mFOLFIRINOX) with or without atezolizumab. Positive results from this combination will bolster our opportunity in pancreatic cancer and potentially provide an additional registrational opportunity. The initial efficacy results from this cohort are expected in the second half of 2025.

Anticipated upcoming milestones
•H1 2025: Initiate registrational study of pelareorep + paclitaxel in HR+/HER2- metastatic breast cancer
•H1 2025: Safety run-in data from cohort 5 of the GOBLET study, investigating pelareorep and mFOLFIRINOX with or without atezolizumab in newly diagnosed pancreatic cancer
•H1 2025: updated efficacy data from cohort 4 of the GOBLET study, investigating pelareorep and atezolizumab in second-line or later anal cancer
•H2 2025: Initial efficacy results from cohort 5 of the GOBLET study, investigating pelareorep and mFOLFIRINOX with or without atezolizumab in newly diagnosed pancreatic cancer

On October 4, 2024 Oxcia reported that it has chosen to re-prioritize the clinical development of OXC-101 from solid tumors to hematological cancers, specifically acute myeloid leukemia (AML) (Press release, Oxcia, OCT 4, 2024, View Source;utm_medium=rss&utm_campaign=oxcia-is-focusing-the-development-of-oxc-101-on-hematological-cancers [SID1234647036]). The preclinical program for OXC-101 has shown good results in both AML and other forms of hematological cancers, and data to date from the phase I/II study MAATEO confirm the previous results. Oxcia has initiated an expansion part of the MAATEO study in patients with refractory/relapsed AML (R/R AML), where OXC-101 is administered in combination with idarubicin (an anthracycline).

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– The first AML patient to be treated with OXC-101 in an innovative combination treatment has recently been recruited, which is very exciting, says Oxcia’s CEO Ulrika Warpman Berglund. We aim to accelerate patient recruitment, for instance by including more study centers in AML, e.g. Rigshospitalet in Copenhagen. We are also working on an ODD (Orphan Drug Designation) application.

Biostock has today published an article describing Oxcia’s investment in AML and IPF, see Oxcias vd om satsningen på AML och lungfibros – BioStock (Oxcia’s CEO on the investment in AML and pulmonary fibrosis – BioStock – only available in Swedish)

Until now, OXC-101 has also been evaluated in the MASTIFF study, a phase I/II study in severely ill patients with an expansion group focused on advanced ovarian cancer and prostate cancer. OXC-101 demonstrated a clear clinically relevant effect, halting cancer growth in a majority of patients. At the same time, some patients suffered dose-limiting side effects in the form of neutropenia.

– Neutropenia means a decrease in neutrophil granulocytes, a type of white blood cell that is important for the immune system. We are now conducting preclinical studies to better understand these mechanisms. Next, we will investigate which doses, indications and patient groups we could proceed with in solid tumors. However, the focus of Oxcia’s development is on AML emphasizes CEO Ulrika Warpman Berglund.