On October 17, 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 preliminary revenue results for the third quarter of 2024, achieving $11.2 million, which included the recording of $10.0 million in U.S. revenue from the commercialization of HEPZATO KIT (Press release, Delcath Systems, OCT 17, 2024, View Source [SID1234647246]).

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The announcement of the recording of $10.0 million in U.S. quarterly revenue from the commercialization of HEPZATO KIT effectively triggers the exercise of Tranche B warrants issued in the previously announced March 29, 2023 Private Investment in Public Equity (the "PIPE"). Holders of the Tranche B warrants from the PIPE have 21 days from the date of this announcement to exercise their Tranche B warrants to purchase shares of common stock at an effective price of $6.00 per share of common stock for an aggregate exercise price of up to approximately $25 million.

"This revenue milestone is an important indicator of the strong demand for HEPZATO KIT, highlighting the unmet medical need it addresses in uveal melanoma patients with liver metastases and the rapid uptake by physicians," said Gerard Michel, Chief Executive Officer of Delcath. "The Company will utilize the additional $25 million of financing to support the ongoing commercial launch and invest in new clinical trials to expand indications which we plan to initiate in 2025."

Final financial results for the third quarter and a detailed business update will be provided during Delcath’s quarterly financial results release and investor call scheduled for November 8, 2024.

On October 17, 2024 Breakpoint Therapeutics GmbH ("Breakpoint"), a company dedicated to the discovery and development of drugs targeting the DNA Damage Response (DDR), reported that it will present preclinical data from its polymerase theta (Pol θ / POLQ) inhibitor programme in a poster at the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium on Molecular Targets and Cancer Therapeutics, being held October 23-25, 2024 in Barcelona, Spain (ENA 2024) (Press release, Breakpoint Therapeutics, OCT 17, 2024, View Source [SID1234647244]).

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DNA polymerase theta is a DNA repair enzyme that is largely absent in normal cells but displays aberrant expression in multiple cancer types which often correlates with poor prognosis. Inhibition of Pol θ is a validated therapeutic modality in certain tumour-specific contexts.

Details of the presentation are as follows:

Abstract Title: Discovery and characterisation of DNA polymerase theta inhibitors for the treatment of cancer

Date: Friday, 25 October, 2024

Time: 9:00 a.m. – 3:00 p.m. CEST

Session Title: DNA Repair Modulation (e.g. PARP, CHK, ATR, ATM)

Abstract Number: 339

Poster Board Number: PB327

On October 17, 2024 Aura Biosciences, Inc. (NASDAQ: AURA), reported positive early data from an ongoing Phase 1 clinical trial of bel-sar (AU-011) in patients with NMIBC. To date, the trial includes 13 patients, with the primary endpoints of evaluating the safety and feasibility of local administration of bel-sar alone (n=5) and bel-sar with light activation (n=8) (Press release, Aura Biosciences, OCT 17, 2024, View Source [SID1234647243]). The secondary endpoints are to evaluate biological activity and immune mediated changes in the tumor microenvironment (TME). 10 of 13 study participants had low grade disease, approximating the 70% incidence of this patient population among all NMIBC patients. The other 3 study participants had high grade disease. In patients receiving bel-sar with light activation (n=8), 4 out of 5 patients with low grade disease demonstrated a clinical complete response with no tumor cells remaining on histopathological evaluation. 2 out of 3 patients with high grade disease demonstrated visual tumor shrinkage observed on cystoscopy. Aura will host a Virtual Urologic Oncology Investor Event at 4:30 pm ET today.

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"We are highly encouraged by this positive early data, which shows that bel-sar has the potential to be a transformative cancer treatment," said Sabine Brookman-May, MD, FEBU, Senior Vice President, Therapeutic Area Head Urologic Oncology of Aura Biosciences. "A potentially differentiating aspect of this novel treatment is the rapid tumor response accompanied by an immune oncology (IO) effect such as a marked CD8+ T-cell infiltration observed in just a matter of days with a single low dose. We believe this could have the potential to translate into a durable response. In parallel with expanding the ongoing Phase 1 trial, we are preparing for a Phase 2 trial to further evaluate bel-sar’s clinical activity and durability of response."

"Bel-sar has the potential to change the treatment paradigm for NMIBC," said Neal Shore, MD, FACS, Medical Director, Carolina Urologic Research Center, AUC Urology Specialists. "Based on this early data, bel-sar’s positive clinical activity and evidence of a bladder urothelial field effect with a single dose, may position bel-sar to be the first immune ablative treatment option for early-stage bladder cancer patients delivered with an in-office procedure."

Bel-sar is a virus-like drug conjugate, designed to have a dual mechanism of action, that induces direct tumor cell necrosis and elicits a robust and durable anti-tumor immune response.

Trial Design: The ongoing Phase 1 trial (NCT05483868) is a two-part, open-label clinical trial, designed to assess the safety and feasibility of bel-sar as a monotherapy. The study treatment is administered 7 to 12 days before the scheduled transurethral resection of bladder tumor (TURBT), the standard of care procedure. The participants are followed for safety monitoring over a 56-day period. The trial is also evaluating bel-sar’s biological activity with histopathological evaluation of tissue samples collected at the time of TURBT (regardless of tumor response) with evaluation of focal necrosis and immune changes in the tumor microenvironment. Part 1 (n=5) of the trial is complete, with patients receiving a single bel-sar dose without light activation. Part 2 (n=10) of the trial is ongoing. 8 patients with a confirmed tumor at time of treatment have received either 100ug or 200ug of bel-sar as a single dose. Of these 8 patients, 5 had low grade disease and 3 had high grade disease. 7 of these 8 patients had a history of recurrent bladder cancer and had undergone multiple TURBTs and adjuvant treatments such as Bacillus Calmette-Guerin (BCG), mitomycin, gemcitabine, cetrelimab and tamoxifen prior to trial enrollment. In the Phase 1 trial expansion, Aura plans to test additional doses and treatment regimens.

Safety Data: In the safety analysis as of the September 9, 2024 data cut-off date (n=12), bel-sar was well-tolerated, with less than 10% of patients reporting Grade 1 and no Grade 2 or higher drug-related adverse events reported. No serious adverse events have been reported. No significant differences between the light-activated and non-light activated cohorts have been observed.

Biological Activity: The data in these 8 patients receiving bel-sar with light activation showed clinical activity detectable as soon as 7 days after a single low dose of bel-sar with light activation. This was demonstrated by histopathological evidence of clinical complete response, necrosis, immune activation or visual tumor shrinkage observed on cystoscopy. For this analysis, "clinical complete response" was defined as the absence of tumor cells on histopathologic evaluation. Of the patients with low-grade disease, 4 out of 5 exhibited a clinical complete response (1 of 4 based on local pathology with central review ongoing), with no tumor cells detected in histopathological evaluation post-treatment in the target and in several non-target bladder tumors. 2 of 3 of the patients with high grade disease demonstrated visual tumor shrinkage observed on cystoscopy, while tumor cells were still present on histopathological evaluation. Immune activation was noted in all patients in both treated target and untreated non-target bladder tumors with infiltration of effector CD8+ and CD4+ T-cells (where immune staining was available). This data provides evidence of a bladder urothelial field effect with a single low dose of bel-sar with light activation, potentially indicating a broader immune response in the bladder beyond the target tumor in these patients.

Aura Virtual Urologic Oncology Investor Event

Aura will host a Virtual Urologic Oncology Investor Event featuring Max Kates, MD (Johns Hopkins), Joe Jacob, MD (Syracuse University), Neal Shore, MD (Carolina Urologic Research Center) and Gary Steinberg, MD (RUSH University) to discuss the early Phase 1 data on Thursday, October 17, 2024, at 4:30 pm Eastern Time. To register for the event, click here. A live question and answer session will follow the formal discussion.

The live webcast of Aura’s Virtual Urologic Oncology Investor Event will be available on the "Investors & Media" page under the "Events & Presentations" section of Aura’s website at View Source, where a replay of the webcast will be archived for 90 days following the presentation date.

On October 17, 2024 British techbio innovator Etcembly reported that it is teaming up with researchers and clinicians from the University of Surrey to launch a groundbreaking new study that could transform the future of cancer treatment. By analysing the immune cells of cancer survivors, this research is set to reveal untapped targets that could deliver the next generation of immunotherapies (Press release, Etcembly, OCT 17, 2024, View Source [SID1234647242]).

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In recent years, treatments that harness a patient’s own immune system to fight cancer have become a key pillar of oncology. However, these drugs don’t work for all, and a wider range of novel immunotherapies is urgently needed.

T cells – specialised immune cells that recognise and destroy cancer – are a vital part of the immune response against the disease. However, the specific molecules that these cells target within tumours remain unclear.

This collaboration between Etcembly and Dr Nicola Annels at the University of Surrey, together with Professor Hardev Pandha at the Royal Surrey Hospital, will take a fresh approach to finding these targets by analysing samples from patients who have survived various cancers for more than three years.

By uncovering the molecules that T cells use to recognise and destroy cancer cells, the team hopes to unlock novel targets for breakthrough treatments, including Etcembly’s own pipeline of immunotherapies.

At the heart of the study are T cell receptors (TCRs) and antibodies, which immune cells use to find and destroy tumours. Etcembly will use their proprietary single-cell sequencing technology and AI-driven analytical platform, EMLyTM, to analyse millions of TCRs and antibodies in blood and tumour samples taken from patients with complete or near-complete responses to immunotherapy.

By harnessing the unparalleled capabilities of large language models (LLMs) – a form of generative AI – and advanced structural modelling, the team aims to identify tumour-reactive receptors and trace them back to the molecules that they are detecting within cancer cells. The team expects to pinpoint and prioritise these targets within 12 to 18 months, accelerating the development of life-saving treatments for patients worldwide.

Nick Pumphrey, Chief Scientific Officer at Etcembly, said, "We’re delighted to collaborate with the team at the University of Surrey on this pioneering research project. By studying people who are surviving cancer, we can identify TCRs and targets that have already proven to be effective, giving us a blueprint to develop a new generation of life-saving immunotherapies."

Hardev Pandha, Professor of Medical Oncology at the University of Surrey and Royal Surrey NHS Foundation Trust, added, "Immunotherapy has been transformational in the field of oncology this last decade. Studying the immune system, and in particular the tumour immune microenvironment, in these responder patients using Etcembly’s approach will be strongly supported by patients to accelerate the development of potent immunotherapies applicable to a wide range of cancers."

On October 17, 2024 Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company committed to advancing new medicines for patients with cancer, reported updated data from the Phase 2 RAMP 201 (ENGOTov60/GOG3052) clinical trial evaluating the combination of avutometinib, an oral RAF/MEK clamp, and defactinib, an oral, selective FAK inhibitor, in patients with recurrent low-grade serous ovarian cancer (LGSOC) (Press release, Verastem, OCT 17, 2024, View Source [SID1234647232]). The data were published as a late-breaking abstract and additional detailed findings will be presented today in an oral plenary session at the International Gynecologic Cancer Society (IGCS) 2024 Annual Meeting in Dublin, Ireland.

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The primary analysis of the RAMP 201 trial, with a data cutoff of June 30, 2024, showed a confirmed overall response rate (ORR) by blinded independent central review (BICR) of 31% (34/109; 95% CI: 23-41) in all evaluable patients with measurable disease with approximately 12 months of follow up. Among patients with KRAS mutant (mt) LGSOC, the confirmed ORR was 44% (25/57; 95% CI: 31-58) and for patients with KRAS wild-type (wt) LGSOC the confirmed ORR was 17% (9/52; 95% CI: 8-30). The median duration of response (DOR) was 31.1 months (95% CI: 14.8-31.1) in all evaluable patients, with 31.1 months (95% CI: 14.8-31.1) in the KRAS mt population and 9.2 months (95% CI: 5.5-NEi) in the KRAS wt population. The median progression-free survival (PFS) was 12.9 months (95% CI: 10.9-20.2) in all evaluable patients, with 22 months (95% CI: 11.1-36.6) in the KRAS mt population and 12.8 months (95% CI: 7.4-18.4) in the KRAS wt population. The disease control rate (DCR) at 6 or more months was 61% in the total evaluable population, 70% in KRAS mt population and 50% in KRAS wt population. The updated data continue to demonstrate avutometinib in combination with defactinib is generally well-tolerated, with a 10% discontinuation rate due to adverse events (AEs) and no new safety signals were identified. The most common treatment-related AEs (all grades, grade ≥3) for the combination were nausea (67.0%, 2.6%), diarrhea (58.3%, 7.8%), and increased blood creatine phosphokinase levels (60.0%, 24.3%).

"The notable response rates and low discontinuation rate seen with the combination of avutometinib and defactinib are significant. These updated results confirm the potential of this new combination therapy to change practice and be the new standard for care for recurrent low-grade serous ovarian cancer, which previously had limited effective treatment options," said Professor Susana Banerjee, M.B.B.S., M.A., Ph.D., F.R.C.P., Global Lead investigator of the study, Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust and Team Leader in Women’s Cancers at The Institute of Cancer Research, London.

Regulatory Update

A Type A meeting was recently held with the U.S. Food and Drug Administration (FDA), during which the Company aligned with the FDA on the Company’s plans to complete the New Drug Application (NDA) submission in October 2024 for adult patients with recurrent KRAS mt LGSOC, who received at least one prior systemic therapy, based on the mature data from the RAMP 201 trial. The Company plans to seek Accelerated Approval from the FDA and request Priority Review. At this time, the FDA did not recommend pursuing a KRAS wt indication under Accelerated Approval. This strategic approach allows the Company to potentially reach the market more efficiently while mapping out a path forward with the FDA for the KRAS wild-type indication, including leveraging data from the ongoing RAMP 301 Phase 3 trial. RAMP 301, which is currently enrolling patients with recurrent LGSOC regardless of KRAS mutation status, will serve as a confirmatory study for the initial indication and has potential to expand the indication regardless of KRAS mutation status.

"In the mature data from the RAMP 201 trial most patients achieved tumor reductions and a median progression-free survival that was greater than one year across both KRAS mutant and KRAS wild-type patient populations. These results reinforce our confidence in the potential of the combination of avutometinib and defactinib to change how patients with recurrent low-grade serous ovarian cancer are treated," said John Hayslip, M.D., chief medical officer of Verastem Oncology. "Encouraged by the durable clinical benefit seen in KRAS wild-type patients in RAMP 201 and the poorer prognosis in this subset of patients that are treated with sub-optimal treatment choices today, we believe that this treatment combination will be the preferred treatment option for all subgroups of patients with recurrent low-grade serous ovarian cancer. We are committed to making the combination available to these patients, including working with the FDA to outline a path forward to expand the indication with additional data."

"Now that we have the mature data from the RAMP 201 trial, we are on track to complete our NDA submission for recurrent KRAS mutant low-grade serous ovarian cancer in October," said Dan Paterson, president and chief executive officer of Verastem Oncology. "We look forward to working with the FDA to potentially bring the first and only FDA-approved treatment specifically for patients with recurrent KRAS mutant low-grade serous ovarian cancer to the U.S. market in 2025."

Conference Call and Webcast Information

Verastem will hold an investor conference call and webcast on October 17, 2024 at 4:30 p.m. EDT, to review the mature data from the RAMP 201 trial. To access the conference call, please dial (844) 763-8274 (local) or (412) 717-9224 (international) at least 10 minutes prior to the start time and ask to be joined into the Verastem Oncology conference call. A live audio webcast of the call, along with accompanying slides, will be accessible under "Events & Presentations" in the Investors & Media section of the company’s website at www.verastem.com.

The Company expects to file a current report on Form 8-K with the Securities and Exchange Commission (SEC) later today, which will include a copy of the IGCS oral presentation and the presentation which the Company intends to use on the investor conference call and webcast.

About RAMP 201

RAMP 201 (ENGOTov60/GOG3052) is an adaptive, two-part multicenter, parallel cohort, randomized, open-label trial to evaluate the efficacy and safety of avutometinib alone and in combination with defactinib in patients with recurrent low-grade serous ovarian cancer. The first part of the study (Part A) determined the selection of the go forward regimen, which was the combination of avutometinib and defactinib versus avutometinib alone, based on overall response rates. The expansion phases of the trial (Parts B and C) are evaluating the safety and efficacy of the go forward regimen of avutometinib 3.2 mg twice weekly and defactinib 200 mg twice daily. The Part D portion of the trial is evaluating a low dose of avutometinib in combination with defactinib to inform individualized dose reduction.

About Low-Grade Serous Ovarian Cancer (LGSOC)

LGSOC is a rare ovarian cancer that is insidious, persistent and ultimately fatal. LGSOC is distinct and different from high-grade serous ovarian cancer (HGSOC) and requires different treatment. LGSOC is highly recurrent and less sensitive to chemotherapy compared to HGSOC. Approximately 6,000-8,000 women in the U.S. and 80,000 worldwide are living with this disease. LGSOC affects younger women with bimodal peaks of diagnosis at ages between 20-30 and 50-60 and has a median survival of approximately ten years. The majority of patients report a negative impact of LGSOC on their mental and physical health, fertility, and long-term quality of life. The current standard of care for this disease includes hormone therapy and chemotherapy, but there are no treatments specifically approved by the U.S. Food and Drug Administration to treat LGSOC.

About the Avutometinib and Defactinib Combination

Avutometinib is a RAF/MEK clamp that induces inactive complexes of MEK with ARAF, BRAF and CRAF potentially creating a more complete and durable anti-tumor response through maximal RAS/MAPK pathway inhibition. In contrast to currently available MEK-only inhibitors, avutometinib blocks both MEK kinase activity and the ability of RAF to phosphorylate MEK. This unique mechanism allows avutometinib to block MEK signaling without the compensatory activation of MEK that appears to limit the efficacy of other MEK-only inhibitors.

Verastem Oncology is currently conducting clinical trials with avutometinib in RAS/MAPK driven tumors as part of its Raf And Mek Program or RAMP. Verastem is currently enrolling patients and activating sites for RAMP 301 (NCT06072781) an international Phase 3 confirmatory trial evaluating the combination of avutometinib and defactinib, a selective FAK inhibitor, versus standard chemotherapy or hormonal therapy for the treatment of recurrent low-grade serous ovarian cancer (LGSOC). RAMP 201 (NCT04625270) is a Phase 2 registration-directed trial of avutometinib in combination with defactinib in patients with recurrent LGSOC and enrollment has been completed for the RAMP 201 trial.

Verastem initiated a rolling New Drug Application (NDA) submission in May 2024 to the U.S. Food and Drug Administration (FDA) for the investigational combination of avutometinib and defactinib in adults with recurrent KRAS mutant LGSOC who received at least one prior systemic therapy and expects to complete its NDA submission in the second half of 2024 with a potential FDA decision in the first half of 2025. The FDA granted Breakthrough Therapy Designation of the investigational combination of avutometinib and defactinib for the treatment of all patients with recurrent LGSOC after one or more prior lines of therapy, including platinum-based chemotherapy. Avutometinib alone or in combination with defactinib was also granted Orphan Drug Designation by the FDA for the treatment of LGSOC.

Verastem Oncology has established clinical collaborations with Amgen and Mirati to evaluate LUMAKRAS (sotorasib) in combination with avutometinib and defactinib and KRAZATI (adagrasib) in combination with avutometinib in KRAS G12C mutant NSCLC as part of the RAMP 203 (NCT05074810) and RAMP 204 (NCT05375994) trials, respectively. The RAMP 205 (NCT05669482), a Phase 1b/2 clinical trial evaluating avutometinib and defactinib with gemcitabine/nab-paclitaxel in patients with front-line metastatic pancreatic cancer, is supported by the PanCAN Therapeutic Accelerator Award. FDA granted Orphan Drug Designation to avutometinib and defactinib combination for the treatment of pancreatic cancer.