On October 7, 2021 Aileron Therapeutics (Nasdaq: ALRN), a chemoprotection oncology company focused on fundamentally transforming the experience of chemotherapy for cancer patients, reported that new preclinical data at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) 2021 on ALRN-6924, currently in development as a novel, selective chemoprotective agent (Press release, Aileron Therapeutics, OCT 7, 2021, View Source [SID1234590934]). The new data demonstrated ALRN-6924’s activity as a radioprotective agent in preclinical mouse models of acute radiation-induced toxicity, leveraging the same mechanism of action – p53 activation and subsequent p21 upregulation as well as p21-induced cell cycle arrest – that has clinically shown protection against chemotherapy-induced toxicities.

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"Like chemotherapy, ionizing radiation is associated with serious, often dangerous side effects, as both chemotherapy and radiation destroy normal, healthy cells," said Manuel Aivado, M.D., Ph.D. "While preliminary, these new preclinical data suggest that ALRN-6924’s mechanism of action, which has demonstrated protection against chemotherapy-induced toxicities of the bone marrow, may also protect against radiation-induced toxicities. Furthermore, these preclinical studies provide our first evidence of ALRN-6924-mediated activation of p21 in epithelial mucosa cells in the GI tract, protecting irradiated mice from body weight loss, and the potential of ALRN-6924 to protect multiple tissues beyond the bone marrow from both chemotherapy and radiation-induced toxicities."

Dr. Aivado continued, "Developing ALRN-6924 as a selective chemoprotective agent in p53-mutated cancers continues to be our chief priority. Nonetheless, these encouraging preclinical data signal a potential future secondary application of ALRN-6924 complementing our ongoing chemoprotection program, and we look forward to conducting more research to further explore that possibility."

Aileron is currently developing ALRN-6924, a first-in-class MDM2/MDMX dual inhibitor, to selectively protect healthy cells in patients with cancers that harbor p53 mutations to reduce or eliminate chemotherapy-induced side effects while preserving chemotherapy’s attack on cancer cells. ALRN-6924 is designed to activate p53 in normal cells, which in turn upregulates p21, which pauses cell cycle in normal, healthy, proliferating cells but not in p53-mutated cancer cells.

In the AACR (Free AACR Whitepaper)-NCI-EORTC poster titled, "The Investigational Chemoprotection Drug ALRN-6924, a Dual Inhibitor of MDMX and MDM2, Shows Potential for Radioprotection" (Poster #P211), Aileron presented the results of preclinical studies designed to evaluate whether p53 activation with ALRN-6924 may protect healthy, proliferating cells in normal tissues from radiation-induced cellular toxicity.

In a non-lethal radiation exposure model, mice were exposed to a single dose of abdominally targeted radiation at 15 Gy following one or more doses/schedules of ALRN-6924 or placebo and then monitored for body weight. Aileron evaluated serum levels of macrophage inhibitory cytokine-1 (MIC-1), a biomarker of p53 activation, as well as biomarkers of p53-mediated cell cycle arrest (p21), and of apoptosis (cleaved poly-ADP-ribose polymerases, or cPARP) in mouse bone marrow and GI tract tissue. Repeated doses of ALRN-6924 administered every eight hours yielded sustained MIC-1 elevation, which correlated with increased p21 positivity in the bone marrow and intestine, while treatment-dependent changes in cPARP expression were minimal. Additionally, mice treated with ALRN-6924 had less radiation-induced body-weight loss than untreated mice. Mice receiving one or more doses of ALRN-6924 eight hours prior to irradiation had an average of 4% body weight loss, while placebo-treated mice had 10% to 15% body weight loss five days after irradiation. The poster will be archived on the Scientific Publications page of Aileron’s website at: View Source

Aileron is currently conducting a Phase 1b randomized, double-blind, placebo-controlled study of ARLN-6924 as a chemoprotective agent in the United States and Europe. The study is enrolling patients with advanced p53-mutated non-small cell lung cancer undergoing treatment with first-line carboplatin plus pemetrexed with or without immunotherapy. The company is pursuing a clinical development strategy designed to advance its vision to bring selective chemoprotection to all patients with p53-mutated cancer regardless of type of cancer or chemotherapy.

On October 7, 2021 Gossamer Bio, Inc. (Nasdaq: GOSS), a clinical-stage biopharmaceutical company focused on discovering, acquiring, developing and commercializing therapeutics in the disease areas of immunology, inflammation and oncology, reported that it will host a conference call and webcast for investors and analysts on Monday, October 11, 2021, at 2:30 pm ET to announce its next clinical product candidates (Press release, Gossamer Bio, OCT 7, 2021, View Source [SID1234590955]).

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Gossamer management will present and discuss its forthcoming additions to its clinical product candidate pipeline. As part of the event, Gossamer Bio management will be available for questions.

Conference Call and Webcast

Gossamer will host a conference call and live audio webcast at 2:30 pm ET on Monday, October 11. The live audio webcast may be accessed through the "Events / Presentations" page in the "Investors" section of the Company’s website at www.gossamerbio.com. Alternatively, the conference call may be accessed through the following:

Conference ID: 4165598
Domestic Dial-in Number: (833) 646-0603
International Dial-in Number: (929) 517-9782
Live Webcast: View Source

A replay of the audio webcast will be available for 30 days on the "Investors" section of the Company’s website, www.gossamerbio.com.

On October 7, 2021 Clovis Oncology, Inc. (NASDAQ: CLVS) reported that nonclinical data describing the expression of fibroblast activating protein (FAP) in a variety of solid tumor types will be presented during the AACR (Free AACR Whitepaper)-NCI-EORTC Virtual AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper), taking place October 7-10, 2021 (Press release, Clovis Oncology, OCT 7, 2021, View Source [SID1234590920]). The analysis, conducted with its partner 3B Pharmaceuticals GmbH, measured FAP expression in multiple tumor types using immunohistochemistry (IHC) as well as the correlation between FAP expression by IHC and in vitro binding of FAP-2286, Clovis’ peptide-targeted radionuclide therapy (PTRT) clinical development candidate that targets FAP.

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"We believe these findings across multiple solid tumor types demonstrate the importance of FAP as a cancer target and underscore the potential for 177Lu-FAP-2286 to treat patients with FAP-expressing tumors," said Dr. Thomas Harding, Executive Vice President and Chief Scientific Officer of Clovis Oncology. "These provide additional validation for our ongoing Phase 1/2 LuMIERE clinical trial of FAP-2286, the first peptide-targeted radionuclide therapeutic in clinical development targeting FAP, and support investigation of FAP-2286 in a broad number of cancer indications. This is representative ofour commitment to emerge as a leader in targeted radionuclide therapy by developing innovative radiotherapies such as FAP-2286 for patients with hard-to-treat cancers."

To determine FAP protein expression in different tumor types, a pan-tumor IHC screen was performed that included 360 samples representing 16 different tumor types. For this analysis, high FAP expression was defined as an overall H-score ≥30 in more than 30% of the samples analyzed in a given tumor type. The IHC screen showed high FAP expression in nine of the 16 solid tumor types evaluated, including pancreatic ductal adenocarcinoma, cancer of unknown primary, salivary gland, mesothelioma, colon, bladder, sarcoma, squamous non–small cell lung, and squamous head and neck cancers. High FAP expression was detected in both primary and metastatic tumor samples and was independent of tumor stage or grade.

The analysis also demonstrated that in most tumor types, FAP expression was predominantly localized to the stroma surrounding the tumor cells within the tumor microenvironment. FAP expression in tumor cells was also observed: in cancers of mesenchymal origin, such as sarcoma and mesothelioma, tumor-cell expression was common, consistent, and strong; in cancers of epithelial origin, tumor-cell FAP expression was rare and, when present, appeared weaker than in the adjacent stroma.

A significant correlation was seen between FAP expression observed by IHC and in vitro FAP-2286 binding as determined by autoradiography, suggesting that FAP is an attractive target for PTRT in a wide array of tumor types.

Following are details of the Clovis-sponsored presentation:

Poster Number: LBA032 – Pan-Cancer Analysis of Fibroblast Activation Protein Alpha (FAP) Expression to Guide Tumor Selection for the Peptide-Targeted Radionuclide Therapy FAP-2286

Lead author: Tanya T. Kwan, PhD

Category: Radiotherapeutics

Date/Time: Thursday, October 7 at 9:00 am ET

The presentation and accompanying poster can also be viewed at: View Source

For more information about FAP-2286, Targeted Radionuclide Therapy (TRT), or Clovis’ TRT development program CLICK HERE.

About FAP-2286

FAP-2286 is a clinical candidate under investigation as a peptide-targeted radionuclide therapy (PTRT) and imaging agent targeting fibroblast activation protein (FAP). FAP-2286 consists of two functional elements; a targeting peptide that binds to FAP and a site that can be used to attach radioactive isotopes for imaging and therapeutic use.High FAP expression has been shown in pancreatic ductal adenocarcinoma, cancer of unknown primary, salivary gland, mesothelioma, colon, bladder, sarcoma, squamous non–small cell lung, and squamous head and neck cancers. High FAP expression was detected in both primary and metastatic tumor samples and was independent of tumor stage or grade. Clovis holds US and global rights for FAP-2286 excluding Europe, Russia, Turkey, and Israel.

FAP-2286 is an unlicensed medical product.

About Targeted Radionuclide Therapy

Targeted radionuclide therapy is an emerging class of cancer therapeutics, which seeks to deliver radiation directly to the tumor while minimizing delivery of radiation to normal tissue. Targeted radionuclides are created by linking radioactive isotopes, also known as radionuclides, to targeting molecules (e.g., peptides, antibodies, small molecules) that can bind specifically to tumor cells or other cells in the tumor environment. Based on the radioactive isotope selected, the resulting agent can be used to image and/or treat certain types of cancer. Agents that can be adapted for both therapeutic and imaging use are known as "theranostics." Clovis, together with licensing partner 3B Pharmaceuticals, is developing a pipeline of novel, targeted radiotherapies for cancer treatment and imaging, including its lead candidate, FAP-2286, an investigational peptide-targeted radionuclide therapeutic (PTRT) and imaging agent, as well as three additional discovery-stage compounds.

About the LuMIERE Clinical Study

LuMIERE is a Phase 1/2 study evaluating FAP-2286 as a peptide-targeted radionuclide therapy (PTRT) targeting fibroblast activation protein, or FAP, in patients with advanced solid tumors (NCT04939610). The Phase 1 portion of the LuMIERE study is evaluating the safety of the investigational therapeutic agent and will identify the recommended Phase 2 dose and schedule of lutetium-177 labeled FAP-2286 (177Lu-FAP-2286). FAP-2286 labeled with gallium-68 (68Ga-FAP-2286) will be utilized as an investigational imaging agent to identify patients with FAP-positive tumors appropriate for treatment with the therapeutic agent. Once the Phase 2 dose is determined, Phase 2 expansion cohorts are planned in multiple tumor types.

On October 7, 2021 IMV Inc. (NASDAQ: IMV; TSX: IMV), a clinical-stage biopharmaceutical company pioneering a novel class of immunotherapies against difficult-to-treat cancers, reported that the immunotherapeutic capabilities of its DPX delivery platform will be featured in two e-poster presentations at the AACR (Free AACR Whitepaper)-NCI-EORTC Virtual AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) October 7-10, 2021 (Press release, IMV, OCT 7, 2021, View Source [SID1234590935]).

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"Collectively, these data demonstrate the versatility and potential of the DPX delivery platform to educate robust, targeted T cell responses to distinct cargo," said Jeremy Graff, Ph.D., Chief Scientific Officer at IMV. "More specifically, the first presentation provides compelling evidence that the DPX technology triggers a more consistent and persistent immune response than conventional emulsions. The second presentation provides the scientific basis for the clinical pursuit of DPX-SurMAGE, a new IMV asset designed to simultaneously elicit immune responses to the survivin and MAGE-A9 proteins, both of which have been implicated in bladder cancer progression."

Yves Fradet, M.D., Professor, Department of Surgery at the Faculty of Medicine, Université Laval in Quebec City commented, "The results obtained with IMV’s dual-targeted DPX-based immunotherapy, DPX-SurMAGE, in preclinical studies are very promising. I believe that patients with bladder cancer will benefit from this treatment while maintaining their quality of life."

Pre-clinical and clinical data presented at the conference show that:

The DPX technology represents a versatile delivery platform that generates robust T cell-based immune responses,
When packaged within the DPX platform, antigenic peptides are delivered and presented to the immune system in a manner that elicits specific T cell-based immune responses that are not achievable with conventional water-based emulsion delivery,
IMV’s lead compound, maveropepimut-S (MVP-S, previously known as DPX-Survivac) is well-tolerated in multiple clinical trials and effectively elicits a specific, robust, and persistent, survivin-specific T cell response evident most prominently in subjects showing greatest clinical benefit,
The DPX delivery platform can be leveraged to incite a T cell response to numerous tumor antigens simultaneously,
IMV’s dual-targeted immunotherapy, DPX-SurMAGE, is well tolerated and generates robust and targeted T cell responses against both survivin and MAGE-A9 peptides in preclinical models.
Collectively, these data provide evidence that the DPX delivery platform is a unique and versatile, immune-educating technology that can be applied in a variety of therapeutic areas where generation of a target-specific immune response is expected to mitigate disease.

Poster Presentation Details

Survivin peptides formulated in the DPX delivery platform rather than standard emulsions, elicit a robust, sustained T cell response to survivin in advanced and recurrent ovarian cancer patients.

Presenter: Yogesh Bramhecha, Ph.D.,
Director, Translational Research, IMV Inc.
Poster Number: LBA026
DPX-SurMAGE, a novel dual-targeted immunotherapy for bladder cancer, induces target-specific T cells with a favorable safety profile in preclinical studies

Presenter: Yves Fradet, M.D.
Professor, Department of Surgery
Faculty of Medicine, Université Laval, Quebec City
Poster Number: LBA030
Full abstracts and e-posters are available on demand on the conference platform. Both e-posters are available under the Scientific Publications & Posters section on IMV’s website.

On October 7, 2021 BeiGene (NASDAQ: BGNE; HKEX: 06160), a global, science-driven biotechnology company focused on developing innovative and affordable medicines to improve treatment outcomes and access for patients worldwide, reported that BRUKINSA (zanubrutinib) has been approved in Australia for the treatment of adult patients with Waldenström’s macroglobulinemia (WM) who have received at least one prior therapy or in first line treatment for patients unsuitable for chemo-immunotherapy (Press release, BeiGene, OCT 7, 2021, View Source [SID1234590956]).1 Following registration of BRUKINSA with the Therapeutic Goods Administration (TGA), these patients will have immediate access to BRUKINSA through a BeiGene sponsored post-approval, pre-reimbursement access program.

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"We are pleased to hear that people living with WM in Australia will have immediate access to this next-generation BTK inhibitor that has demonstrated clinical benefit with potential to improve treatment outcomes."

In addition, BRUKINSA recently received approval from the Singapore Health Sciences Authority (HSA) for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.

"BTK inhibition is an established mode of treatment for patients with WM, and the ASPEN trial showed that BRUKINSA is highly effective and has improved tolerability compared to the first-generation BTK inhibitor," said Professor Con Tam, MBBS, M.D., Disease Group Lead for Low Grade Lymphoma and Chronic Lymphocytic Leukemia at the Peter MacCallum Cancer Centre and a principal investigator on the BRUKINSA clinical program. "BeiGene first began clinical trials of BRUKINSA in Australia in 2013, and since that time, many Australians have benefitted from treatment as part of ongoing clinical studies. We hope this therapy will offer new hope for people living with WM in Australia."

In Australia, more than 6,000 people are diagnosed with non-Hodgkin’s lymphoma (NHL) each year, making it the sixth most common cancer in adults.2 WM is a rare, slow-growing lymphoma that occurs in less than two percent of patients with NHL.3 The disease usually affects older adults and is primarily found in the bone marrow, although it may also impact lymph nodes and the spleen.3

"While WM is a slow-growing lymphoma, not all patients fully respond to existing therapies and many discontinue treatment due to side effects," commented David Young, the National Team Leader at the WMozzies. "We are pleased to hear that people living with WM in Australia will have immediate access to this next-generation BTK inhibitor that has demonstrated clinical benefit with potential to improve treatment outcomes."

BeiGene has submitted for reimbursement of WM to the Pharmaceutical Benefits Advisory Committee (PBAC). In a first for the PBAC, BeiGene expects to enter a facilitated resolution pathway in order to seek a listing date for the WM indication.

"BRUKINSA has been shown to induce deep and durable responses with reduced off-target side effects, suggesting improved clinical benefit compared to standard BTK inhibitor therapy," said Jane Huang, M.D., Chief Medical Officer, Hematology at BeiGene. "We are grateful to the Australian investigators, patients and families who participated in clinical trials contributing to TGA approval. Our ability to offer BRUKINSA to people in Australia impacted by WM is another step toward fulfilling our goal of increasing affordable access to oncology medicines around the world."

"This approval in Australia, and our recent approval in Singapore, represent BRUKINSA’s continued expansion in the APAC region," added Adam Roach, Vice President and Head of Commercial for APAC (ex-Greater China) at BeiGene. "We have been building commercial teams in these markets to support our goal of bringing this potential best-in-class BTK inhibitor to patients who need them globally."

The Australian registration for BRUKINSA in WM is based on efficacy results from the ASPEN clinical trial, a Phase 3 randomised, open-label, multicentre trial (NCT03053440) that evaluated BRUKINSA compared to ibrutinib in patients with relapsed or refractory (R/R) or treatment-naïve (TN) WM who harbor a MYD88 mutation (MYD88MUT). In the ASPEN trial, BRUKINSA demonstrated a numerically higher very good partial response (VGPR) rate (28.4%, 95% CI: 20, 38) compared to ibrutinib (19.2%, 95% CI: 12, 28), although the primary endpoint of statistical superiority related to deep response (VGPR or better) was not met.

In the ASPEN trial, of the 101 patients with WM randomized and treated with BRUKINSA, 5% of patients discontinued due to adverse events, including cardiomegaly, neutropenia, plasma cell myeloma, and subdural haemorrhage. Adverse events leading to dose reduction occurred in 14.9% of patients, with the most common being neutropenia (3.0%) and diarrhea (2.0%).

The overall safety profile of BRUKINSA is based on pooled data from 779 patients with B-cell malignancies treated with BRUKINSA in clinical trials. The most common adverse reactions (≥20%) with BRUKINSA were neutropenia, thrombocytopenia, upper respiratory tract infection, haemorrhage/haematoma, rash, bruising, anaemia, musculoskeletal pain, diarrhea, pneumonia, and cough. The most common Grade 3 or higher adverse reactions (≥5%) were neutropenia, thrombocytopenia, pneumonia, and anaemia.

The recommended dose of BRUKINSA is either 160 mg twice daily or 320 mg once daily, taken orally with or without food. The dose may be adjusted for adverse reactions and reduced for patients with severe hepatic impairment and certain drug interactions.

About BRUKINSA (zanubrutinib)

BRUKINSA is a small molecule inhibitor of Bruton’s tyrosine kinase (BTK) discovered by BeiGene scientists that is currently being evaluated globally in a broad clinical program as a monotherapy and in combination with other therapies to treat various B-cell malignancies. Because new BTK is continuously synthesised, BRUKINSA was specifically designed to deliver complete and sustained inhibition of the BTK protein by optimising bioavailability, half-life, and selectivity. With differentiated pharmacokinetics compared to other approved BTK inhibitors, BRUKINSA has been demonstrated to inhibit the proliferation of malignant B cells within a number of disease relevant tissues.

BRUKINSA is approved in the United States, China, Australia, Canada, and other international markets in selected indications and under development for additional approvals globally.

BeiGene Oncology

BeiGene is committed to advancing hematology, immuno-oncology and targeted therapies in order to bring impactful and affordable medicines to patients across the globe. We have a growing R&D team of approximately 2,300 colleagues dedicated to advancing more than 90 clinical trials involving more than 13,000 patients and healthy subjects. Our expansive portfolio is directed by a predominantly internalised clinical development team supporting trials in more than 40 countries or regions. We currently market three medicines discovered and developed in our labs: BTK inhibitor BRUKINSA in the United States, China, Canada, and additional international markets; and non-FC-gamma receptor binding anti-PD-1 antibody tislelizumab and PARP inhibitor pamiparib in China. BeiGene has a high quality, innovative science and medicine organisation and is a leader in China with a large oncology focused commercial team.

BeiGene also partners with innovative companies who share our goal of developing therapies to address global health needs. We commercialise a range of oncology medicines in China licensed from Amgen and Bristol Myers Squibb. We also plan to address greater areas of unmet need globally through our collaborations including with Amgen, Bio-Thera, EUSA Pharma, Mirati Therapeutics, Seagen, and Zymeworks. BeiGene has also entered into a collaboration with Novartis granting Novartis rights to develop, manufacture, and commercialise tislelizumab in North America, Europe, and Japan.