On September 12, 2024 Elevar Therapeutics, Inc., a majority-owned subsidiary of HLB Co., Ltd., reported the presentation of three posters at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2024 in Barcelona, Spain, Sept. 13-17 (Press release, Elevar Therapeutics, SEP 12, 2024, View Source [SID1234646530]).

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"The results to be presented at ESMO (Free ESMO Whitepaper) continue to support the safety and efficacy of rivoceranib in combination with camrelizumab as a first-line systemic treatment option for patients with hepatocellular carcinoma; as well as the potential of combining rivoceranib with other immune checkpoint inhibitors as a therapeutic option for many types of solid tumors," commented Chris Galloway, M.D., senior vice president of clinical and medical affairs at Elevar Therapeutics.

Camrelizumab and rivoceranib were granted Orphan Drug Designation by the U.S. Food and Drug Administration and the European Medical Association.

ESMO Presentation 985P (Abstract 5451): Analysis of antidrug antibodies (ADA) to camrelizumab in CARES-310: The pivotal phase III study of camrelizumab + rivoceranib in unresectable hepatocellular carcinoma (uHCC)

The poster reports an analysis of antidrug antibodies (ADAs) in the CARES-310 (NCT03764293) Phase 3 clinical study for the treatment of unresectable hepatocellular carcinoma (uHCC). There was minimal impact of ADAs on PK, efficacy and safety. Therefore, follow-up monitoring of ADAs to cam is not warranted.

CARES-310 was the first trial to demonstrate significant progression-free survival (PFS) and overall survival benefits with immunotherapy plus an anti-angiogenic tyrosine kinase inhibitor (TKI) over standard TKI as a first-line treatment for uHCC.

Speaker: Ahmed O. Kaseb (Houston, United States of America) Onsite poster display date: Mon., Sept. 16 Link to Abstract 5451 / Presentation 985P

ESMO Presentation 963P (Abstract 5635): Quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis to assess the impact of treatment with camrelizumab + rivoceranib (cam+rivo) on quality-of-life vs sorafenib (sora) in patients (pts) with unresectable hepatocellular carcinoma (uHCC): Study CARES-310

The poster reports results from Phase 3 CARES-310 study, concluding cam + rivo had clinically meaningful quality-adjusted survival benefits over sorafenib. The higher incidence of adverse effects in patients treated with cam + rivo was likely due to longer time on treatment versus sorafenib.

Speaker: Andrew Moon (Chapel Hill, United States of America) Onsite poster display date: Mon., Sept. 16 Link to Abstract 5635 / Presentation 963P

ESMO Presentation 1013P (Abstract 2318): A phase I study of rivoceranib combined with nivolumab in patients with unresectable or metastatic cancer

The poster reports results from Phase 1 (NCT03396211) clinical study of rivoceranib plus nivolumab (rivo + nivo) in patients with advanced metastatic solid tumors. The study concluded that rivo + nivo demonstrated a manageable safety profile and promising antitumor efficacy across many solid tumors as measured by reduction in tumor burden over time. Further studies are needed to confirm the safety and efficacy of rivo + nivo therapy.

Speaker: Neal S. Chawla (Duarte, United States of America) Onsite poster display date: Sat., Sept. 14 Link to Abstract 2318 / Presentation 1013P

About Hepatocellular Carcinoma

More than 800,000 people worldwide are diagnosed with liver cancer each year. Liver cancer is a leading cause of cancer accounting for more than 700,000 deaths annually.[i] Hepatocellular Carcinoma (HCC) is the most common type of primary liver cancer. It most frequently develops in people with chronic underlying liver inflammation which may be from viral and non-viral causes. HCC typically has a poor prognosis with limited treatment options and continues to be a diagnosis with an ongoing urgent medical need.

About Rivoceranib

Rivoceranib, a small-molecule tyrosine kinase inhibitor (TKI), is a highly potent inhibitor of vascular endothelial growth factor receptor (VEGFR), a primary pathway for tumor angiogenesis. VEGFR inhibition is a clinically validated target to limit tumor growth and disease progression. Rivoceranib is currently being studied as a monotherapy and in combination with chemotherapy and immunotherapy in various solid tumor indications. Ongoing clinical studies include uHCC (in combination with camrelizumab), gastric cancer (as a monotherapy and in combination with paclitaxel), adenoid cystic carcinoma (as a monotherapy) and colorectal cancer (in combination with Lonsurf). Rivoceranib was the first TKI approved in gastric cancer in China (November 2014). It is also approved in China in combination with camrelizumab as a first-line treatment for uHCC (January 2023). The drug has been studied in more than 6,000 patients worldwide and was well tolerated in clinical trials with a comparable safety profile to other TKIs and VEGF inhibitors. Orphan drug designations have been granted in gastric cancer (U.S., EU and South Korea), in adenoid cystic carcinoma (U.S.) and in uHCC (U.S. and EU). Elevar Therapeutics, Inc. holds the global rights (excluding China) to rivoceranib and has partnered for its development and marketing with HLB-LS in South Korea. Rivoceranib, under the name apatinib, is also approved in China for advanced gastric cancer and in second-line advanced HCC by the Chinese -territory license-holder, Jiangsu Hengrui Pharmaceuticals Company Ltd., (Hengrui Pharma), under the brand name Aitan.

About Camrelizumab

Camrelizumab (SHR-1210) is a humanized monoclonal antibody that binds to the programmed death-1 (PD-1) receptor. Blockade of the PD-1/PD-L1 signaling pathway is a therapeutic strategy showing success in a wide variety of solid and hematological cancers. Camrelizumab is developed by Hengrui Pharma and has been studied in more than 5,000 patients. Currently, 50 clinical trials are underway in a broad range of tumors (including liver cancer, lung cancer, gastric cancer, and breast cancer, etc.) and treatment settings. Camrelizumab, under the brand name AiRuiKa, is currently approved for eight indications in China, including monotherapy for the treatment of HCC (second-line), in combination with rivoceranib as a treatment for uHCC (first-line), relapsed/refractory classic Hodgkin’s lymphoma (third-line), esophageal squamous cell carcinoma (second-line) and nasopharyngeal carcinoma (third-line or further) and in combination with chemotherapy for the treatment of non-small cell lung cancer (non-squamous and squamous), esophageal squamous cell carcinoma and nasopharyngeal carcinoma in the first-line setting. The U.S. Food and Drug Administration granted Orphan Drug Designation to camrelizumab for advanced HCC in April 2021 and by the EMA in August 2024.

In October 2023, Elevar licensed camrelizumab, an anti-PD-1 antibody, for commercialization from Jiangsu Hengrui Pharmaceuticals Co., Ltd. (Hengrui Pharma) worldwide excluding Greater China and Korea.

On September 12, 2024 Aura Biosciences, Inc. (NASDAQ: AURA), a clinical-stage biotechnology company developing precision therapies for solid tumors designed to preserve organ function, reported positive Phase 2 end of study results evaluating bel-sar (AU-011) for the first-line treatment of early-stage choroidal melanoma (CM), a vision and life-threatening ocular cancer (Press release, Aura Biosciences, SEP 12, 2024, View Source [SID1234646529]). The results were presented at The Retina Society Annual Meeting, on Thursday, September 12, 2024, in Lisbon, Portugal.

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The Phase 2 study (NCT04417530) is an open-label, ascending single and repeat dose escalation trial in patients with early-stage CM (small CM and indeterminate lesions) designed to evaluate the safety, tolerability, and efficacy of up to three cycles of bel-sar treatment. The trial included both single and multiple ascending dose cohorts, with a total of 22 patients enrolled. Patients were closely monitored over a twelve-month follow-up period to assess tumor control, visual acuity preservation, and tumor growth rate.

Tumor Control and Visual Acuity Preservation

The Phase 2 results demonstrated that bel-sar achieved an 80% tumor control rate (n=8/10) among Phase 3-eligible patients who received the therapeutic regimen, with complete cessation of growth following treatment among responders (post-treatment average growth rate of 0.011 mm/yr among responders compared to 0.351 mm/yr prior to study entry; p<0.0001). Visual acuity preservation was achieved in 90% of these 10 patients. Importantly, 80% of these 10 patients were at high risk for vision loss with tumors close to the fovea or optic disc, highlighting the potential for vision preservation with this novel class of drugs. Of note, the current standard of care is radiotherapy, which leads to visual acuity of <20/200 (the cutoff for legal blindness) in the treated eye in up to 87% of patients.1 The Phase 2 results are a significant achievement considering the typically poor prognosis associated with choroidal melanoma, a rare and life-threatening ocular cancer, where there are no approved vision-preserving therapies to date.

Highly Favorable Safety Profile with No Dose-Limiting Toxicities

The safety profile of bel-sar was highly favorable in all participants regardless of dose. There were no treatment-related serious adverse events (SAEs) reported. Ocular treatment-related AEs (TRAEs) were mild (Grade 1), included anterior chamber inflammation (18%) or cell (9%) and resolved without

sequelae. The vast majority (~70%) of the anterior chamber inflammation/cell events were self-limited, requiring no treatment, and resolved in a median of 6 days. For those events that did require treatment, topical steroid eye drops, administered for a median of 6 days, achieved complete resolution of the inflammation. Eye pain occurred in 9% of patients and was mild (Grade 1). Importantly, no treatment-related posterior inflammation events (no vitritis, choroiditis, retinitis, retinal pigment epithelium changes, or vasculitis) were reported.

"Many patients with early-stage choroidal melanoma currently face the difficult choice of whether to treat the cancer and risk losing their vision in the treated eye, or delay treatment and risk the tumor progressing," said Dr. Ivana Kim, Director of the Ocular Melanoma Center, Mass Eye and Ear / Harvard Medical School. "The Phase 2 end of study data that I presented at The Retina Society Annual Meeting showed 80% tumor control rate, 90% vision preservation, and a highly favorable safety profile in early-stage CM. Bel-sar has the potential to become the first treatment that achieves the dual goals of treating the tumor while also preserving vision, which could change the treatment paradigm for patients with this disease."

"We believe these Phase 2 results provide clinical evidence for bel-sar as a potential vision-sparing, first-line treatment option for patients with early-stage CM," said Dr. Jill Hopkins, Chief Medical Officer and President of Research and Development at Aura Biosciences. "Bel-sar is potentially a first-in-class novel therapy and we are excited to continue to advance this program, which is currently enrolling patients in our ongoing global Phase 3 CoMpass trial."

Aura received written agreement from the U.S. Food and Drug Administration (FDA) under a Special Protocol Assessment (SPA) for the design and planned analysis of the global Phase 3 CoMpass trial indicating concurrence by the FDA with the adequacy of the study, if successful, to address the objectives necessary to support Aura’s planned biologics license application submission. Aura Biosciences is focused on enhancing treatment options and improving outcomes for patients with CM and other cancers.

Aura Virtual Ocular Oncology Investor Event

Aura will host a virtual ocular oncology investor event featuring Dr. Ivana Kim, MD (Mass Eye and Ear) and Dr. Prithvi Mruthyunjaya, MD, MHS (Stanford University Byers Eye Institute) to discuss the Phase 2 end of study data on Thursday, September 12, 2024, at 8:00 am 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 ocular 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 September 12, 2024 Sanofi reported that it has entered into an exclusive licensing agreement with RadioMedix, Inc., a US clinical-stage biotechnology company developing radiopharmaceuticals for PET imaging and targeted alpha therapy (TAT) against unmet medical needs in cancer, and Orano Med, a French clinical-stage biotechnology company, subsidiary of the Orano Group, developing lead-212 (212Pb) radioligand therapies (RLTs) against cancer (Press release, Sanofi, SEP 12, 2024, View Source [SID1234646528]).

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This collaboration between Sanofi, RadioMedix and Orano Med focuses specifically on the late-stage project, AlphaMedixTM (212Pb-DOTAMTATE), which currently is being evaluated for the treatment of adult patients with unresectable or metastatic, progressive somatostatin-receptor expressing neuroendocrine tumors (NETs), a rare cancer. AlphaMedixTM is a TAT which consists of a somatostatin receptor-targeting peptide complex radiolabeled with lead-212 (212Pb) that serves as an in vivo generator of alpha particles.

Dietmar Berger
Chief Medical Officer, Global Head of Development, Sanofi
"We are excited to develop a leading-edge project in the rapidly evolving field of radioligand therapies in rare cancers. Early results for 212Pb have demonstrated its differentiated biophysical and clinical profile, reinforcing its potential to be a transformative radioligand therapeutic for patients across multiple difficult-to-treat rare cancers. This agreement underscores our efforts to explore innovative collaborations that leverage novel technologies to address the needs of people living with cancer."

AlphaMedixTM has recently been granted Breakthrough Therapy Designation in gastroenteropancreatic neuroendocrine tumors (GEP-NETs) from the US Food and Drug Administration (FDA) for patients who are naïve to peptide-receptor radionuclide therapy. The FDA’s decision was based on findings from phase 1i and 2 clinical studies, which found that AlphaMedixTM was well tolerated and provided substantial reduction in tumor burden, with a durable response rate (ORR according to RECIST 1.1) of 62.5%.i AlphaMedixTM is currently completing phase 2 clinical development, and the data is being discussed with the FDA for potential regulatory filing and approval.

Ebrahim S. Delpassand
Chairman and CEO, RadioMedix
"The Breakthrough Therapy Designation of AlphaMedix is a testament of its success in validating targeted alpha therapies. We see this as a potential for the future of nuclear oncology in general, and today it is pioneering next-generation treatment for patients with neuroendocrine tumors. In our research, we have seen that significantly higher energy delivery over much shorter path lengths in the tissue of alpha emitters can overcome the limitations of currently available beta emitter radioligand therapies. We believe 212Pb is an ideal alpha emitter with highly desirable physical and supply characteristics in comparison to other alpha emitters. RadioMedix has been one of the pioneers in the field of radioligand therapy in the U.S and, through this licensing agreement with Sanofi, our goal is to bring this potentially life-saving therapy to as many patients as possible."

Julien Dodet
President and CEO, Orano Med
"At Orano Med, we are at the forefront of innovation in radioligand therapy and are developing a global industrial platform for the manufacture and distribution of our 212Pb-conjugated drugs. This marks a pivotal moment to expedite the development of this new therapy and in our fight against cancer. Through this agreement, we aim to lead the charge in advancing radioligand therapies with the ambition to revolutionize cancer therapeutics."

Under the licensing agreement, Sanofi will be responsible for the global commercialization of AlphaMedixTM, while Orano Med will be responsible for the manufacturing of AlphaMedixTM through its global industrial platform currently under development. Under the terms of the agreement, RadioMedix and Orano Med will receive an upfront payment of €100 million and up to €220 million in sales milestones and be eligible for tiered royalties. This agreement is subject to standard regulatory approvals required for transactions of this nature.

In striving to become the number one immunoscience company globally, Sanofi remains committed to advancing oncology innovation. Through focused strategic decisions the company has reshaped and prioritized its pipeline, leveraging its expertise in immunoscience to drive progress. Efforts are centered on difficult-to-treat cancers such as select hematologic malignancies, and solid tumors with critical unmet needs, including multiple myeloma, acute myeloid leukemia, certain types of lymphomas, as well as gastrointestinal and lung cancers.

About neuroendocrine tumors
Neuroendocrine tumors (NETs) are a heterogeneous group of rare cancers that originate from neuroendocrine cells. These cancers occur mostly in the gastrointestinal tract and pancreas but can also occur in other tissues including the thymus, lung, and other uncommon sites such as ovaries, heart, and prostate. Most NETs strongly express somatostatin receptors. In the United States, around 12,000 patients annually are expected to be diagnosed with neuroendocrine tumors, with an average 5-year survival rate of 60% at a metastatic stage. Despite the global prevalence of NETs increasing each year, it is considered a rare cancer that is estimated to affect approximately 35/100,000 individuals worldwide.

On September 12, 2024 Epitopea, a transatlantic cancer immunotherapeutics company developing accessible off-the-shelf RNA-based immunotherapies, reported it has been awarded a grant of just over £500,000 (approximately $658,000 USD) from Innovate UK (Press release, Epitopea, SEP 12, 2024, View Source [SID1234646527]).

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Epitopea was selected to receive funding from Innovate UK’s £12 million Cancer Therapeutics programme (1), which will provide a non-dilutive grant in support of research that is aimed at developing both therapeutic vaccines and T cell receptor-based therapies targeting antigens that are differentially presented by stromal cells. This class of therapies has the potential to impact patient outcomes given the well-established role of stromal cells in thwarting a therapeutic response to many established therapies.

The antigens in question were discovered by Epitopea’s CryptoMapTM platform, which enables targeting of a new class of untapped tumor specific antigens, known as CryptigenTM TSAs, that are broadly shared across multiple patients with the same tumor type. Epitopea intends to leverage these aberrantly expressed CryptigenTM TSAs to expand its therapeutic pipeline of RNA immunotherapies aimed at extending the durability of patient responses.

Dr. Jon Moore, Epitopea’s CSO, said:

"We believe better cancer therapies are needed to transform the lives of patients, especially in hard-to-treat solid tumors where overall survival can still be poor. Targeting stromal cells with immunotherapeutics represents an attractive and highly differentiated approach that we believe may translate into a deeper, more durable therapeutic response. We are therefore delighted that we have secured this grant support from Innovate UK’s Cancer Therapeutics programme, in recognition of our work developing life-changing cancer therapeutics."

Dr Karen Spink, Head of Medicines at Innovate UK, said:

"We are excited to see the diversity of businesses that have been supported through our Cancer Therapeutics programme. The industry-led R&D projects will advance transformative treatments for a range of cancers. This portfolio of investments will diversify the pipeline of targeted, safe, and effective therapies for cancer patients."

On September 12, 2024 Clarity Pharmaceuticals (ASX: CU6) ("Clarity", "the Company"), a clinical stage radiopharmaceutical company with a mission to develop next-generation products that improve treatment outcomes for children and adults with cancer, reported an update on the safety review of the first 3 participants enrolled in cohort 4 of the SECuRE trial who received 2 doses of 67Cu-SAR-bisPSMA (Press release, Clarity Pharmaceuticals, SEP 12, 2024, View Source [SID1234646526]). Cohort 4 is the final cohort in the dose escalation phase of the study, with participants receiving a minimum of 2 and a maximum of 4 doses of 67Cu-SAR-bisPSMA at 12GBq.

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The SECuRE trial (NCT04868604)1 is a Phase I/IIa theranostic trial for identification and treatment of participants with prostate-specific membrane antigen (PSMA)-expressing metastatic castrate-resistant prostate cancer (mCRPC) using 64Cu/67Cu-SAR-bisPSMA. 64Cu-SAR-bisPSMA is used to visualise PSMA-expressing lesions and select candidates for subsequent 67Cu-SAR-bisPSMA therapy. The trial is a multi-centre, single arm, dose escalation study with a cohort expansion involving approximately 44 participants in the US and Australia. The overall aim of the trial is to determine the safety and efficacy of 67Cu-SAR-bisPSMA for the treatment of prostate cancer.

Cohort 4 is the first to explore the safety and anti-cancer effects of multiple therapy cycles of 67Cu-SAR-bisPSMA at the highest dose of 12GBq. This is the last cohort of the dose escalation phase, before the trial advances into its Phase II stage (cohort expansion) in 14 participants, pending safety evaluation.

Cohort 4 is designed as a "3+3" cohort, where participants will receive a minimum of 2 therapy cycles. Based on the positive safety profile observed in the first 3 cohorts of the SECuRE trial, a change to the dosing schedule of cohort 4 from "2 doses" to "up to 4 doses" has previously been approved by the SRC. This will allow participants who are benefiting from 67Cu-SAR-bisPSMA to receive 2 additional doses under the SECuRE trial (up to 4 doses in total) (Figure 1).

Safety & Efficacy
The SRC has reviewed the safety data of the first 3 participants of cohort 4 who have received 2 cycles of 67Cu-SAR-bisPSMA, and no DLTs have been observed to date. Two participants have completed the DLT period, and 1 participant will complete the DLT period by the end of September. Almost all AEs were mild to moderate, with the majority having resolved or improved at the last assessment. In the final participant who is yet to complete the DLT period, the only AE reported to date was nausea, which has resolved.

Early preliminary efficacy assessment shows a reduction in PSA levels following treatment in both participants who have completed the DLT period. In the weeks following the last therapy dose, these participants have already exhibited PSA drops of more than 60%. The largest drop in PSA to date was a fall of 92.3% (from a baseline PSA of 157.4 ng/mL), and it continues to decline based on the latest assessment. This participant, who had failed several lines of therapy prior to receiving 67Cu-SAR-bisPSMA (i.e. androgen deprivation therapy [ADT], androgen receptor pathway inhibitor [ARPI] and an investigational agent through a clinical trial), has already had a radiographic partial response based on Response Evaluation Criteria in Solid Tumours v1.1 (RECIST) assessment, with a reduction of 60.6% in tumour volume evaluated by PSMA positron emission tomography (PET) imaging thus far (Figure 2).