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 IMMUNOPRECISE ANTIBODIES LTD. (the "Company" or "IPA") (NASDAQ: IPA) (TSX VENTURE: IPA) and the Pierre Fabre pharmaceutical group reported that IPA’s subsidiary, Talem Therapeutics LLC ("Talem"), and Pierre Fabre have entered a multi-year, multi-target research collaboration with the goal to discover and develop therapeutics antibodies for up to nine targets (Press release, ImmunoPrecise Antibodies, OCT 7, 2021, View Source [SID1234590933]). This strategic collaboration is expected to help expand Talem’s portfolio of novel antibodies across oncology. It adds to the variety of diverse relationships that the IPA group of companies holds across the pharmaceutical and biotechnology sector.

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Under the research collaboration, scientists from both companies will work together and contribute their respective resources to discover and develop novel antibodies leveraging the IPA group’s antibody discovery technologies, such as B cell Select or Deep Display using wild-type and/or transgenic animals, available human libraries, as well as their signature "end-to-end" services. The antibodies developed in the research collaboration against the selected targets will be jointly owned by Talem and Pierre Fabre and, following the completion of each target specific research program, Pierre Fabre will have an option to obtain an exclusive worldwide license to Talem’s interest in those jointly discovered antibodies against that particular target, and Talem would be eligible to receive certain up-front and contingent downstream payments. In addition, if licensed, Pierre Fabre will be responsible for the preclinical and clinical development, as well as the commercialization of the jointly discovered antibodies.

"Less than two years ago we started Talem Therapeutics to provide a unique partnering opportunity for companies to jointly seek the development of promising novel candidates," stated Dr. Stefan Lang, Chief Business Officer of ImmunoPrecise. "We are very excited to join forces with Pierre Fabre, combining our advanced antibody technologies with their world-class expertise in immuno-oncology is a powerful strategic combination enabling the teams to jointly address life threatening human diseases."
"Drug discovery in immuno-oncology is a priority for Pierre Fabre. We are therefore very pleased to enter this multi-target research collaboration. Talem will provide us with its expertise and a variety of technology platforms to enable the discovery of therapeutic antibodies, towards a set of structurally diverse targets." added Francesco Hofmann, Head of R&D at Pierre Fabre Medical Care.

On October 7, 2021 Nuvalent, Inc., (Nasdaq: NUVL), a biopharmaceutical company focused on creating precisely targeted therapies for clinically proven kinase targets in cancer, reported that new preclinical data on Thursday supporting advancement of its parallel lead programs in non-small cell lung cancer (NSCLC) (Press release, Nuvalent, OCT 7, 2021, View Source [SID1234590932]). NVL-520, a ROS1-selective inhibitor, and NVL-655, an ALK-selective inhibitor, were specifically designed to solve for the dual challenges of kinase resistance and selectivity which limit the activity and durability of currently available cancer therapies.

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The data are available via three on-demand "short-talk" posters at the 2021 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), which runs from Oct. 7 through Oct. 10. The presentations detail additional preclinical evidence that NVL-520 and NVL-655 1) were active against both wild-type and various known resistance variants of ROS1 or ALK, respectively; 2) were brain-penetrant with the potential to address brain metastases; and 3) selectively inhibited their targets compared to the structurally related tropomyosin receptor kinase B (TRKB), thereby minimizing the potential for off-target TRKB-related central nervous system (CNS) adverse events. The posters will also be available on the Nuvalent website.

"The Nuvalent discovery team operates under an ethos of thorough investigation, with the goal of ensuring that we nominate drug candidates that best embody the product profiles we have defined in close collaboration with physician-scientists," said Henry Pelish, Ph.D., Vice President of Biology at Nuvalent and a presenting poster author. "This is exemplified in our approach to comprehensive in vitro characterization of target selectivity compared to the structurally similar kinase TRKB during the discovery and early development of both NVL-520 and NVL-655, which we detail here.

"Our physician-scientist collaborators are instrumental not only in helping us to identify the desired product characteristics that we believe are most impactful to treatment paradigms today, but also in furthering the investigation of our compounds," continued Dr. Pelish. "It has been a privilege to work closely alongside Dr. Aaron Hata’s group at Mass General Cancer Center to generate the new data presented here in support of the broad preclinical activity of NVL-520 against ROS1 wild type and resistance variants. We look forward to continued collaboration as we work to advance NVL-520 and NVL-655 into clinical studies, and further mature our discovery programs."

Aaron N. Hata, M.D., Ph.D., is a Nuvalent scientific advisor and co-author whose lab at Mass General Cancer Center in Boston focuses on advancing targeted therapies for patients with lung cancer.

"Resistance mutations, off-target adverse events, and brain metastases present significant challenges in the development of the next-generation of targeted therapies for kinases such as ROS1 and ALK," said Dr. Hata. "I am encouraged by the growing body of preclinical data showing that both NVL-520 and NVL-655 maintained selective inhibition of their targets even in the presence of a wide variety of resistance mutations and displayed the important combination of both TRKB selectivity and brain penetrance to open up the potential to treat brain metastases while avoiding off-target CNS adverse events. Together, this combination of characteristics may have the potential to drive more durable responses for patients."

The U.S. Food and Drug Administration has cleared the company’s Investigational New Drug application for NVL-520. Nuvalent plans to initiate the Phase 1 portion of a First-in-Human (FIH) Phase 1/2 clinical trial for NVL-520 in patients with advanced ROS1-positive NSCLC and other solid tumors in the second half of 2021. Nuvalent plans to initiate the Phase 1 portion of a FIH Phase 1/2 clinical trial investigating NVL-655 in advanced ALK-positive NSCLC and other cancers during the first half of 2022.

AACR-NCI-EORTC Presentation Overview:

*Presenting author

Title: Preclinical Antitumor Activity of NVL-520 in Patient-Derived Models Harboring ROS1 Fusions, Including G2032R Solvent Front Mutation
Authors: Amit Deshpande, Satoshi Yoda, Anupong Tangpeerachaikul, Nancy E. Kohl, Joshua C. Horan, Aaron N. Hata, Henry E. Pelish*
Poster Number: P249

Summary of Presentation:

NVL-520 is a potent, highly selective, and brain-penetrant ROS1 inhibitor as previously demonstrated by in vitro and in vivo studies.
NVL-520 demonstrated potent activity against multiple additional ROS1+ NSCLC patient-derived in vitro cell line (PDC) and in vivo xenograft (PDX) models.
Activity was observed irrespective of fusion partner and against both the wild-type and TKI-resistant solvent front mutation (G2032R) ROS1 kinase domain.
Pharmacodynamic analysis of tumors from mice treated with NVL-520 revealed a dose-dependent reduction in ROS1 levels, markers of downstream signaling, and cell proliferation across multiple models of ROS1-driven disease.
Title: NVL-655 Exhibits Antitumor Activity in Lorlatinib-Resistant Subcutaneous and Intracranial Models of ALK-Rearranged NSCLC
Authors: Anupong Tangpeerachaikul*, Amit Deshpande, Nancy E. Kohl, Joshua C. Horan, Henry E. Pelish
Poster Number: P244

Summary of Presentation:

NVL-655 is a potent and brain-penetrant ALK inhibitor as demonstrated by activity in a mouse intracranial tumor model study.
NVL-655 showed activity against a wide variety of ALK mutations, particularly G1202R+ mutations, whether as a single mutation (G1202R) or as compound mutations (G1202R/L1196M and G1202R/G1269A).
Activity was observed both in vitro and in vivo across various contexts, including fusion partners, EML4 breakpoint variants, and tumor contexts.
Title: Evaluating TRKB Activity of Novel Preclinical Brain-Penetrant ROS1 and ALK Inhibitors
Authors: Anupong Tangpeerachaikul*, Joshua C. Horan, Henry E. Pelish
Poster Number: P247

Summary of Presentation:

TRKB-related central nervous system adverse events present a key challenge for the development of brain-penetrant ROS1 and ALK therapies, as both on-target kinases exhibit ~70% kinase domain similarity to the off-target TRKB.
Nuvalent devised a multi-assay approach to evaluate TRKB inhibition and guide the discovery of selective ROS1 and ALK inhibitors, with the goal of minimizing adverse events and driving durable responses for patients.
Leveraging multiple biochemical and cell-based assays increases confidence that results are reproducible across various biological contexts.
All examined assays indicated that NVL-520 and NVL-655 were highly selective for their wild-type and treatment-resistant oncogenic targets over TRKB.

On October 7, 2021 – SELLAS Life Sciences Group, Inc. (NASDAQ: SLS) ("SELLAS" or the "Company"), a late-stage clinical biopharmaceutical company focused on developing novel cancer immunotherapies for a broad range of indications, reported that Angelos Stergiou, MD, ScD. h.c., President and Chief Executive Officer of SELLAS, will participate in two upcoming conferences:

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Laguna Biotech CEO Forum 2021 to be held at the Montage Laguna Beach hotel in Laguna Beach, CA on October 10-12, 2021.

A.G.P./Alliance Global Partners Biotech & Specialty Pharma Conference to be held virtually on Wednesday, October 13, 2021.
For more information about the conferences, or to schedule a one-on-one meeting with SELLAS management, please contact your representative directly, or send an email to A.G.P./Alliance Global Partners at [email protected], or KCSA Strategic Communications at [email protected].

On October 7, 2021 Y-mAbs Therapeutics, Inc. ("Y-mAbs" or the "Company"), NASDAQ: YMAB), a commercial-stage biopharmaceutical company focused on the development and commercialization of novel, antibody-based therapeutic products for the treatment of cancer, reported that the U.S. Food and Drug Administration ("FDA") has granted Rare Pediatric Disease Designation ("RPDD") for the Company’s lutetium labelled omburtamab antibody program for the treatment of medulloblastoma (Press release, Y-mAbs Therapeutics, OCT 7, 2021, View Source [SID1234590930]).

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177Lu-omburtamab-DTPA, a monoclonal B7-H3 antibody that has been radiolabeled with lutetium-177, is currently in a multicenter Phase 1 clinical trial in pediatric patients with refractory medulloblastoma, and in a multicenter Phase 1 clinical trial targeting B7-H3 positive CNS/LM tumors in adults. We believe that both indications address clear unmet medical needs.

"The RPDD makes us eligible for a Priority Review Voucher ("PRV") upon potential approval of the biologics license application for this rare pediatric cancer. Among our leading compounds under development, four now have RPDDs, and this designation for 177Lu-omburtamab-DTPA further increase our chances of ultimately receiving multiple PRVs," said Thomas Gad, founder, Chairman and President.

Dr. Claus Moller, Chief Executive Officer further notes, "We are dedicated to bring 177Lu-omburtamab-DTPA to patients who desperately need alternative methods of treatment. We are very pleased by this recognition by the FDA and look forward to expanding the ongoing Phase 1 studies with 177Lu-omburtamab-DTPA into separate Phase 2 arms."

Researchers at Memorial Sloan Kettering Cancer Center ("MSK") developed omburtamab, which is exclusively licensed by MSK to Y-mAbs. As a result of this licensing arrangement, MSK has institutional financial interests in the product.