On April 11, 2022 aTyr Pharma, Inc. (Nasdaq: LIFE), a biotherapeutics company engaged in the discovery and development of innovative medicines based on novel biological pathways, reported a poster presentation at the 2022 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, which is being held April 8 – 13, 2022, in New Orleans, LA, and virtually (Press release, aTyr Pharma, APR 11, 2022, View Source [SID1234611983]). The poster and corresponding abstract are available for browsing on the AACR (Free AACR Whitepaper) website through July 13, 2022. The poster is also available on the aTyr website.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The poster presents findings from a preclinical study, conducted in collaboration with Dr. Arthur M. Mercurio and his lab at the University of Massachusetts Medical School, characterizing the subtypes of breast cancer that are most responsive to treatment with ATYR2810, a fully humanized monoclonal antibody that selectively and functionally blocks the interaction between neuropilin-2 (NRP2) and VEGF by directly binding at the site of the VEGF binding pocket. Interrogation of ATYR2810 activity in combination with chemotherapy across a panel of breast cancer cells lines using an in vitro 3D colony formation assay revealed that highly aggressive and more mesenchymal cell lines associated with metastasis, including triple negative breast cancer (TNBC), were most responsive. Data from both patient derived organoid and patient derived xenograft models from TNBC where ATYR2810 demonstrated anti-tumor activity showed downregulation of key genes known to promote metastasis and drug resistance, including CXCR4 and a set of genes linked to the process of epithelial-mesenchymal transition (EMT). Furthermore, ATYR2810 monotherapy inhibited spontaneous lung metastasis in an experimental model of TNBC, demonstrating the potential therapeutic effects of blocking the NRP2/VEGF signaling axis on preventing tumor persistence.

"Highly aggressive tumors such as TNBC have been shown to have elevated NPR2 expression and are typically treated with resection and chemotherapy, though the potential for metastasis and tumor regrowth, which is thought to be strongly linked to the process of EMT, is high. The ability of ATYR2810 to downregulate genes associated with EMT, reduce metastasis and enhance chemosensitivity in these highly aggressive subtypes of breast cancer provides valuable insight regarding the types of tumors that may benefit from treatment with ATYR2810," said Leslie A. Nangle, Ph.D., Vice President, Research at aTyr. "These findings suggests that ATYR2810 may serve as a novel therapeutic agent for the treatment of advanced and metastatic cancers. We look forward to advancing ATYR2810 to a Phase 1 study in cancer patients in the second half of the year."

Details of the poster and corresponding abstract are as follows:

Title: ATYR2810, a fully humanized monoclonal antibody targeting the VEGF-NRP2 pathway sensitizes highly aggressive and chemoresistant TNBC subtypes to chemotherapy
Authors: Zhiwen Xu, Alison G. Barber, Christoph Burkart, Hira Lal Goel, Justin Rahman, Kristina Hamel, Zachary Fogassy, Lisa Eide, Clara Polizzi, Jasmine Stamps, Luke Burman, Kaitlyn Rauch, Ann Menefee, Yanyan Geng, Sofia Klopp Savino, Yeeting E. Chong, Darin Lee, Suzanne Paz, Arthur M. Mercurio, Leslie A. Nangle. aTyr Pharma, University of Massachusetts Chan Medical School, Pangu BioPharma, IAS HKUST – Scripps R&D, Hong Kong University of Science and Technology.
Abstract Control Number: 7998
Session Title: Late-Breaking Research: Experimental and Molecular Therapeutics 1 / Chemistry
Session Date and Time: Monday, April 11, 2022 from 1:30PM – 5:00PM ET
Location: New Orleans Convention Center, Exhibit Halls D – H, Poster Section 16
Poster Board Number: 10
Permanent Abstract Number: LB085

About ATYR2810

aTyr is developing ATYR2810 as a potential therapeutic for certain aggressive tumors where neuropilin-2 (NRP2) is implicated. ATYR2810 is a fully humanized monoclonal antibody that is designed to specifically and functionally block the interaction between NRP2 and one of its primary ligands, VEGF. ATYR2810 is the first Investigational New Drug (IND) candidate to arise from aTyr’s in-house research program designing monoclonal antibodies to selectively target the NRP2 receptor and its associated signaling pathways. NRP2 is a cell surface receptor that is highly expressed in certain tumors, in the lymphatic system and on key immune cells implicated in cancer progression. Increased NRP2 expression is associated with worse outcomes in many cancers. Preclinical data suggest that ATYR2810 could be effective against certain types of solid tumors. ATYR2810 is currently undergoing IND-enabling studies.

On April 11, 2022 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) ("Actinium" or the "Company"), a leader in the development of targeted radiotherapies for patients with unmet needs, reported positive results from preclinical studies evaluating an anti-HER3 antibody, conjugated with an Actinium-225 (Ac-225) radioisotope payload, for targeting HER3-positive non-small cell lung cancer (NSCLC) cells (Press release, Actinium Pharmaceuticals, APR 11, 2022, View Source [SID1234611981]). These data were presented at the American Association of Cancer Research (AACR 2022) annual meeting, which is being held April 8th – 13th at the Ernest N. Morial Convention Center in New Orleans, Louisiana.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

AACR Poster Highlights:

Ac-225-HER3 antibody radio conjugate (ARC) eliminated HER3-postive tumors in an in vivo animal model of human non-small cell lung cancer (NSCLC) at multiple dose levels with increased survival
A dose-dependent cytotoxic effect against HER3 expressing cells was observed in vitro with the Ac-225-HER3-ARC
Biodistribution data demonstrates accumulation of the Ac-225-HER3-ARC in HER3 expressing tumors in the in vivo model of NSCLC
Conjugation of Ac-225 to the HER3 antibody did not affect the antibody’s targeting properties as determined by binding to HER3 expressing cells
Dr. Helen Kotanides, Vice President, Translational Research and Preclinical Development, stated, "HER3 is a well-validated target that is overexpressed in a number of cancers and associated with poor survival in breast, ovarian, lung, gastric and prostate cancer. It is also upregulated in response to HER1 and HER2 targeted therapies as part of acquired resistance against these EGFR therapies. These data show that arming a HER3-targeting agent with Actinium-225 results in potent anti-tumor agent, which improved survival in our NSCLC models. These data support our goal of developing a HER3 targeted radiotherapy for use in a patient population in need of new treatments and give us great excitement for our ongoing collaboration with AVEO centered around HER3."

Sandesh Seth, Chairman and CEO of Actinium, stated, "We are excited to continue to demonstrate Actinium’s enhanced R&D capabilities and commitment to developing potent radiotherapies targeting solid tumors. We look forward to sharing these data, which show the efficacy for our novel approach of conjugating Actinium-225 to a HER3 antibody at AACR (Free AACR Whitepaper) 2022. The development of Ac-225-HER3-ARC, a product of our validated Antibody Warhead Enabling (AWE) technology platform, represents a departure from conventional HER3-targeting approaches, such as naked antibodies and antibody drug conjugates, that are currently being explored for this tumor antigen. These exciting data highlight Actinium’s leadership in developing novel targeted radiotherapy approaches for treating cancers having high unmet needs."

The full poster is available as an e-poster on the AACR (Free AACR Whitepaper) 2022 platform and will be presented in-person at the conference with details below:

AACR Poster Details

Title: Targeting HER3 receptor positive cancers with a novel anti-HER3 antibody radioconjugate (ARC)
Session Category: Experimental and Molecular Therapeutics
Session Title: Preclinical Radiotherapeutics
Session Date and Time: Tuesday, April 12, 2022, 1:30 PM – 5:00 PM
Location: New Orleans Convention Center, Exhibit Halls D-H, Poster Section 25
Poster Board Number: 4
Permanent Abstract Number: 3306

The poster will be accessible via Actinium’s website here.

On April 11, 2022 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) ("Actinium" or the "Company"), a leader in the development of targeted radiotherapies for patients with unmet needs, reported that preclinical data highlighting the efficacy of the combination of an anti-HER3 antibody radiation conjugate (ARC) and a CD47 blocking antibody immunotherapy was presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) (AACR 2022) annual meeting, which is being held April 8th – 13th at the Ernest N. Morial Convention Center in New Orleans, Louisiana (Press release, Actinium Pharmaceuticals, APR 11, 2022, View Source [SID1234611980]). Actinium assessed an Actinium-225 (Ac-225)-conjugated anti-HER3 antibody with magrolimab, an anti-CD47 antibody being developed by Gilead Sciences, in HER3-positive preclinical models.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

AACR Poster Highlights:

Dramatic improvement in tumor growth inhibition is observed in vivo with the Ac-225-HER3-ARC and magrolimab combination therapy compared to magrolimab alone
The combination of Ac-225-HER3-ARC and magrolimab significantly enhanced phagocytosis in HER3-positive cells compared to either single agent in vitro
Upregulation of cell surface calreticulin is observed following treatment with 225Ac-HER3-ARC in HER3-positive cell lines
Dr. Helen Kotanides, Vice President, Translational Research and Preclinical Development, said, "We hypothesize that the upregulation of the ‘eat me’ signal, calreticulin, induced by targeted radiotherapy could enhance the immunomodulatory effects of an anti-CD47 antibody, resulting in increased anti-tumor efficacy. These data presented at AACR (Free AACR Whitepaper) corroborate our previous work presented at SITC (Free SITC Whitepaper) and support our rationale in targeting both blood cancer and solid tumors with a CD47 targeted radiotherapy combination. We are highly encouraged by the remarkable improvement in anti-tumor efficacy observed with the combination of an Ac-225-HER3-ARC with magrolimab. Collectively, the in vitro and in vivo data support further investigation of this novel combination and we look forward to continuing to advance the first ever targeted radiotherapy CD47 combinations."

Sandesh Seth, Chairman and CEO of Actinium, said, "We continue to demonstrate the potential of combining targeted radiotherapy with a CD47 blocking antibody immunotherapy such as magrolimab. These results support our vision to develop more effective treatments for cancer patients through the expansion of our pipeline into solid tumors and to develop innovative targeted radiotherapy combinations with immunotherapy leveraging our strong technology platform, IP and clinical experience. We are excited to highlight these results showing the potential for adding Ac-225-HER3 ARC to CD47 antibodies to enhance the latter’s immunotherapeutic efficacy at AACR (Free AACR Whitepaper). These data along with our recent collaborations with EpicentRx and AVEO Oncology give us strong momentum towards the clinic with highly novel CD47-SIRPα combinations and HER3 targeted radiotherapies."

The full poster is available as an e-poster on the AACR (Free AACR Whitepaper) 2022 platform with details below:

AACR Poster Details

Title: Anti-HER3 radioimmunotherapy enhances the anti-tumor effects of CD47 blockade in solid tumors
Session Category: Immunology
Session Title: Immune Checkpoints
Session Date and Time: Sunday, April 10, 2022, 1:30 PM – 5:00 PM
Location: New Orleans Convention Center, Exhibit Halls D-H, Poster Section 38
Poster Board Number: 19
Permanent Abstract Number: 609

The poster will be accessible via Actinium’s website here.

On April 11, 2022 Beyond Cancer, Ltd., an affiliate of Beyond Air, Inc. (NASDAQ: XAIR) that is focused on developing ultra-high concentration nitric oxide (UNO) for the treatment of solid tumors, reported promising new in vivo and in vitro data that support the potential of the company’s novel gaseous nitric oxide (gNO) therapy to treat various types of solid tumors (Press release, Beyond Cancer, APR 11, 2022, View Source [SID1234611979]). These data were presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are excited to present these new data that further support the mode of action for our gNO therapy to treat solid tumors and induce an innate and adaptive immune response. In addition, these new data show a dose dependent response in the ability of gNO to kill various types of cancer cells," stated Dr. Selena Chaisson, Chief Executive Officer and Director. "These new preclinical data for our gNO therapy provide support for the continued advancement of this program, which is on track to initiate a first-in-human study in the first half of 2022."

The in vivo study (abstract 1283) assessing the mode of action following a single 5-minute gNO treatment provided data showing an effect on the primary tumor 14 days post treatment. These data show that intratumoral injection of concentrations of gNO at 20,000 and 50,000 ppm led to increased recruitment of T cells, B cells, macrophages and dendrocytes to the primary tumor. An elevated number of T cells and B cells were also detected in the spleen and blood 21 days following gNO treatment. In addition, at the same timepoint, a marked reduction in the number of myeloid derived suppressor cells was seen in the spleen.

Results from the in vitro study (abstract 1848) show that exposure of six different cancer cell lines – including human ovarian and pancreatic and mouse lung, melanoma, colon, and breast– to ultra-high concentrations of gNO ranging from 10,000 ppm to 100,000 ppm for up to 10 minutes resulted in a dose-dependent cytotoxic response. The higher concentration doses of gNO lead to near instant cell death, while the lower concentration doses required a longer exposure period to elicit cell death. Cell viability was assessed using two assays: XTT and clonogenic assay. After one minute of exposure to 25,000 ppm gNO, less than 10% viability was observed in all cell lines.

"We believe that together with the known ability of nitric oxide to activate and recruit the immune system, the data presented this year at AACR (Free AACR Whitepaper) suggest that gNO may be a potent therapeutic agent for tumor treatment across a range of tumor types. Specifically, we saw gNO induce innate and adaptive immune cell populations and the reduction of immune suppressor cells, which we believe are indicative of an anti-tumor immune response that underlies the rejection of secondary tumors in gNO treated mice. We look forward to continuing to develop this exciting therapy," stated Hila Confino, Chief Scientific Officer of Beyond Cancer.

Dr. Frederick Dirbas, Surgical Oncologist and Associate Professor of Surgery in Stanford’s Department of Surgery and member of the Stanford Cancer Institute, commented, "Immunotherapy has shown so much promise in treating solid tumors that it is exciting to see where Nitric Oxide can potentially fit into this therapeutic space."

The presentations detailing the in vivo and in vitro data presented at the AACR (Free AACR Whitepaper) Annual Meeting, which are titled, "Single intra-tumoral injection of gaseous nitric oxide induces an adaptive immune response in a mouse CT-26 solid tumor model" (abstract 1283) and "Ultra-high concentrations of gaseous nitric oxide show rapid cytotoxic capabilities against colon, breast, pancreatic and other cancer cells in vitro" (abstract 1848) will be made available on the company’s website (click here).

Details of the AACR (Free AACR Whitepaper) presentations are as follows:

Title: 1283 – Single intra-tumoral injection of gaseous nitric oxide induces an adaptive immune response in a mouse CT-26 solid tumor model
Session: Clinical Research Excluding Trials – Immune Mechanisms Invoked by Other Therapies
Location: New Orleans Convention Center, Exhibit Halls D-H, Poster Section 32, Poster Board Number 5 on Monday Apr 11, 2022 9:00 AM – 12:30 PM CST
Participant: Hila Confino, PhD; Chief Scientific Officer, Beyond Cancer

Title: 1848 – Ultra-high concentrations of gaseous nitric oxide show rapid cytotoxic capabilities against colon, breast, pancreatic and other cancer cells in vitro
Session: Experimental and Molecular Therapeutics – Mechanisms of Drug Action 1
Location: New Orleans Convention Center, Exhibit Halls D-H, Poster Section 24, Poster Board Number 20 on Monday Apr 11, 2022 1:30 PM – 5:00 PM CST
Participant: Hila Confino, PhD; Chief Scientific Officer, Beyond Cancer

About Nitric Oxide (NO)
Nitric Oxide (NO) is a powerful molecule, naturally synthesized in the human body, proven to play a critical role in a broad array of biological functions. In the airways, NO targets the vascular smooth muscle cells that surround the small resistance arteries in the lungs. Currently, exogenous inhaled NO is used in adult respiratory distress syndrome, post certain cardiac surgeries, and persistent pulmonary hypertension of the newborn to treat hypoxemia. Additionally, NO is believed to play a key role in the innate immune system and in vitro studies suggest that NO possesses anti-microbial activity not only against common bacteria, including both gram-positive and gram-negative, but also against other diverse pathogens, including mycobacteria, viruses, fungi, yeast, and parasites, and has the potential to eliminate multi-drug resistant strains.

On April 11, 2022 BioCryst Pharmaceuticals, Inc. (Nasdaq: BCRX) reported that the company will present at the 21st Annual Needham Virtual Healthcare Conference on Thursday, April 14, 2022, at 11:45 a.m. ET (Press release, BioCryst Pharmaceuticals, APR 11, 2022, View Source [SID1234611977]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Links to a live audio webcast and replay of the presentation may be accessed in the Investors & Media section of BioCryst’s website at http://www.biocryst.com.