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.

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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.

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"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]).

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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.

On April 11, 2022 SELLAS Life Sciences Group, Inc. (NASDAQ: SLS) ("SELLAS" or the "Company"), a late-stage clinical biopharmaceutical company focused on the development of novel therapies for a broad range of cancer indications, reported that the first acute myeloid leukemia (AML) patient has enrolled in the fifth dose level (22.5mg twice a week) cohort, out of the expected six dose cohorts, in the ongoing Phase 1 dose-escalating clinical trial with SELLAS’ newly in-licensed GFH009 asset (Press release, Sellas Life Sciences, APR 11, 2022, View Source [SID1234611976]). There have been no dose-limiting toxicities, including no grade 3/4 neutropenia (an abnormally low count of a type of white blood cell), in the first four dose levels (2.5mg, 4.5mg, 9mg and 15 mg) with the twice-weekly GFH009 dosing. The last planned dose level in this trial is 30mg.

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Initial data from the first four dose levels show a significant anti-leukemic effect at the 9mg and 15mg dose levels given twice a week in AML patients resistant to the multiple standard-of-care treatments, with two patients refractory to, or relapsed after, venetoclax treatment experiencing greater or equal to a 50 percent decrease in bone marrow blasts following GFH009 monotherapy. Approximately 35 percent of all newly diagnosed AML patients and 50 percent of second-line AML patients are resistant to venetoclax combinations, the current standard of care for treating older and frail AML patients. The two patients each previously had six lines of therapy with venetoclax, chemotherapy and experimental agent combinations. These observed clinical effects are consistent with pre-clinical data showing GFH009’s effectiveness in AML models resistant to venetoclax.

Following the Phase 1 clinical trial’s completion, SELLAS plans to begin a Phase 2 trial with GFH009 in combination with venetoclax and the chemotherapy azacitidine in AML patients. Based on the preclinical results showing a synergy between GFH009 and venetoclax, as well as the initial Phase 1 data in AML patients seen to date, the Company believes that GFH009 has the potential to improve venetoclax’s effectiveness and potentially convert resistance to venetoclax into a response.

"While we continue GFH009’s dose escalation in the Phase 1 study, set to be completed later this year, the initial data is showing great promise in helping to treat AML patients who continue to suffer and are not responding to the standard of care – or, in fact, any available treatment," said Angelos Stergiou, M.D., Sc.D. h.c., President and CEO of SELLAS. "With no emerging safety concerns up to this point, administering GFH009 could potentially lead to a substantial increase in efficacy with a favorable safety profile, especially given the twice-weekly dosing schedule, which differentiates it from other CDK9 inhibitors currently in development, and given its high selectivity. The asset’s strong synergy with venetoclax could also allow it to improve a patient’s response to the current standard of care. We look forward to continuing with the trial and unveiling additional data over time."

CDK9 is a major target for anti-cancer therapeutics. Many cancers depend on rapid protein production to grow and/or protect cancer cells from shutting down once anti-cancer drugs damage them. To forge those proteins, cancer cells depend on CDK9 to allow the RNA transcript elongation, which is necessary for the protein production that keeps cancer growing. By shutting down CDK9, the Company believes GFH009 blocks the cancer-promoting and cancer-protecting protein production, ultimately potentially resulting in cancer cell death.

On April 11, 2022 Seelos Therapeutics, Inc. (Nasdaq: SEEL), a clinical-stage biopharmaceutical company focused on the development of therapies for central nervous system disorders and rare diseases, reported an amendment of the agreement with Phoenixus AG, formerly known as Vyera Pharmaceuticals AG ("Vyera"), for the development of SLS-002 (intranasal racemic ketamine) to repurchase in cash and stock the remaining royalties payable on any future net sales of SLS-002, all future success and commercial based milestones and the change of control fee in the event SLS-002 is acquired (Press release, Apricus Biosciences, APR 11, 2022, View Source [SID1234611975]).

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On March 6, 2018, Seelos entered into an asset purchase agreement (the "Purchase Agreement") with Vyera, currently known as Phoenixus AG, to acquire the assets and liabilities of Vyera’s intranasal racemic ketamine program, which Seelos now calls SLS-002. As additional consideration to certain upfront cash and equity payments and success-based milestone payments contemplated under the prior agreement, Seelos agreed to pay a mid-teens percentage royalty on any future net sales of SLS-002. In February 2021, Seelos amended the asset purchase agreement, for three additional cash payments, agreeing to repurchase 9% of the future royalties and reduce its royalty obligations to a mid-single digit percentage on any future net sales of SLS-002. Seelos completed those payments in February, June, and September of 2021. Under the amendment entered into on April 8, 2022, for additional cash and stock payments due by April 2022, July 2022 and January 2023, the parties have agreed to terminate in full all contingent payment obligations to Vyera and its related entities under the Purchase Agreement, effective upon the payment and issuance of all cash and stock payments.

"We believe this repurchase of the remaining financial obligations owed or that may become payable on SLS-002 has the potential to return meaningful future value to Seelos’ stockholders, assuming we are successful in the clinical development, regulatory approval processes, and commercialization of the intranasal ketamine program," said Raj Mehra, Ph.D., Chairman and CEO of Seelos.

"This amendment removes all future royalties due to Vyera, nearly $100 million of potential future milestones and a change of control fee in the event this program were to be acquired as a standalone transaction or as part of a larger transaction," said Michael Golembiewski, CFO of Seelos.

About SLS-002

SLS-002 is intranasal racemic ketamine with two investigational new drug applications for the treatment

of Acute Suicidal Ideation and Behavior in Major Depressive Disorder or Post-Traumatic Stress Disorder. SLS-002 was originally derived from a Javelin Pharmaceuticals, Inc./Hospira, Inc. program with 16 clinical studies involving approximately 500 subjects. SLS-002 looks to address an unmet need for a therapy to treat suicidality in the U.S. Traditionally, anti-depressants have been used in this setting but many of the existing treatments are known to contribute to an increased risk of suicidal thoughts in some circumstances, and if they are effective, it often takes weeks for the full therapeutic effect to be manifested. The clinical development program for SLS-002 included two parallel healthy volunteer studies (Phase I) and is being followed by pivotal registration studies after meeting with the FDA. Based on information gathered from the databases of the Agency for Healthcare Research and Quality, there were more than 1,000,000 visits to emergency rooms for suicide attempts in 2019 in the U.S. alone. Experimental studies suggest ketamine has the potential to be a rapid, effective treatment for depression and suicidality.