On November 10, 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 combination data that support the potential of the company’s novel gaseous nitric oxide (gNO) therapy to treat various types of solid tumors in combination with immune checkpoint inhibitor (ICI) therapies, including anti-PD-1 (Press release, Beyond Cancer, NOV 10, 2022, View Source [SID1234623764]). These data were published in an abstract by the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) and will be presented in a poster presentation today at the 37th Annual SITC (Free SITC Whitepaper) Meeting in Boston, MA.

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"The results presented this week offer an encouraging first look at the potential synergistic effect of ultra-high concentration nitric oxide (UNO) and anti-PD-1 therapy," stated Dr. Selena Chaisson, Chief Executive Officer and Director. "Immunotherapies are a cornerstone in current treatment options for tumors, and we are excited to see these in vivo data show the ability of a single treatment of UNO when used in combination with anti-PD-1 have a positive impact on tumor regression rates and overall survival. We believe these promising data provide a strong rationale for the continued advancement of this program in combination with immune checkpoint therapies."

"Our previous work has shown the ability of UNO therapy to impart an immune response that is capable of preventing metastases in mice with CT26," stated Hila Confino, Chief Scientific Officer of Beyond Cancer. "Our combination data presented today at the SITC (Free SITC Whitepaper) 2022 Annual Meeting show an effect on the primary tumor and, importantly, can treat metastatic disease and not just prevent it. We look forward to presenting further details on the ability of UNO to stimulate an anti-cancer immune response."

The poster presentation detailing the in vivo combination data presented at the SITC (Free SITC Whitepaper) 2022 Annual Meeting is titled, "Intratumoral Administration of High-Concentration Nitric Oxide and Anti PD-1 Treatment Leads to Higher Tumor Regression Rates and Prolonged Survival in CT26 Tumor-Bearing Mice" (abstract 819). The ePoster with accompanying slides and audio are available on the company’s website (click here).

Details of the Company’s presentation are as follows:

Title: Intratumoral Administration of High-Concentration Nitric Oxide and Anti PD-1 Treatment Leads to Higher Tumor Regression Rates and Prolonged Survival in CT26 Tumor-Bearing Mice

Location: Boston Convention & Exhibition Center, Exhibit Hall C, Abstract 819

Date: Thursday Nov 10, 2022 from 9 a.m.-9 p.m. EST

Participant: Hila Confino, Ph.D; Chief Scientific Officer, Beyond Cancer, Ltd.

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. 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 and adaptive immune system response and in vitro studies suggest that NO possesses broad-spectrum antimicrobial activity and anticancer properties.

On November 10, 2022 Cue Biopharma, Inc. (Nasdaq: CUE), a clinical-stage biopharmaceutical company developing a novel class of injectable biologics to selectively engage and modulate tumor-specific T cells directly within the patient’s body, reported the presentation of new positive data from its ongoing Phase 1 trial evaluating its lead interleukin 2 (IL-2)-based biologic, CUE-101 in combination with pembrolizumab (KEYTRUDA), as a first line therapy for patients with recurrent/metastatic HPV+ head and neck squamous cell carcinoma (HNSCC) (Press release, Cue Biopharma, NOV 10, 2022, View Source [SID1234623763]). The data will be presented in a poster at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s 37th Annual Meeting (SITC 2022), to be held in Boston, Massachusetts and virtually on November 8-12, 2022.

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The poster will also provide an update from the Company’s ongoing fully enrolled Phase 1b trial evaluating CUE-101 monotherapy as third line and beyond therapy in the same patient population. Additionally, the Company will present two posters discussing the design of its ongoing Phase 1 trial evaluating its second IL-2 based candidate, CUE-102, for the treatment of Wilms’ Tumor 1 positive (WT1+) malignancies, and preclinical data regarding its mechanistic effect in vitro and in vivo.

"We are very encouraged with the overall response rate observed in the trial so far with CUE-101, and its potential to improve standard of care for HPV+ head and neck cancer patients," said Dr. Christine Chung, M.D., Chair, Department of Head and Neck-Endocrine Oncology, Moffitt Cancer Center, and a principal investigator participating in the clinical trial. "There is an urgent need for more effective and durable treatment options with less side effects as more than half of all patients with recurrent/metastatic HNSCC given the current standard of care will experience disease progression. I look forward to following this promising CUE-101 clinical data through."

Key data highlights from the CUE-101 dose escalation and patient expansion portion of the Phase 1 trial in combination with pembrolizumab with 16 evaluable patients to date, include:

Overall response rate (ORR) of 40% and a clinical benefit rate (CBR) of 70% in the first 10 evaluable patients treated at the recommended Phase 2 dose (RP2D) of 4 mg/kg of CUE-101 and 200 mg of pembrolizumab administered every three weeks – This includes four confirmed partial responses (cPR) in addition to three durable stable disease (DSD) of ≥ 12 weeks. These responses include patients with low PD-L1 expression (combined positive score (CPS) less than 20).
At the CUE-101 2 mg/kg dose plus pembrolizumab (n=3), one patient experienced a cPR and one DSD, for a CBR of 67%.
At the CUE-101 1 mg/kg dose plus pembrolizumab (n=3), one patient experienced DSD, for a CBR of 33%.
Notably, tumor reduction from baseline in the five patients with confirmed PRs was between 35% and 69%.
Key data highlights from the CUE-101 expansion portion of the Phase 1b trial at the RP2D as a monotherapy to date, include:

42% overall clinical benefit rate, including one PR of > 42 weeks duration and seven DSD.
Median overall survival (mOS) approaching greater than 12 months in third line and beyond (3L+) patients treated with CUE-101 monotherapy, which is 50% greater than current standard of care (SOC) with anti-PD-1 therapies in second line (2L) patients.
CUE-101 continued to show a favorable tolerability profile both as monotherapy and in combination with pembrolizumab.

Ken Pienta, M.D., acting chief medical officer of Cue Biopharma, added, "This new data from our combination study demonstrates early evidence of complementary mechanistic activity of CUE-101 with pembrolizumab. In addition, the sustained clinical benefit rate with CUE-101 as monotherapy is very encouraging and has continued to demonstrate proof-of-concept of CUE-101 as a single agent. Overall, the data shows the potential of CUE-101 to provide patients with an improved clinical benefit rate and with lower toxicity than current standard of care. We look forward to continuing to evaluate data from the trial in addition to defining the potential registrational trial for CUE-101, which we anticipate in mid-2023."

Anish Suri, Ph.D., president and chief scientific officer of Cue Biopharma, said, "Initiation of the Phase 1 trial evaluating our second IL-2-based biologic, CUE-102, is also an important milestone for the company as we continue to demonstrate the versatility and modularity of our platform to potentially treat multiple cancers. CUE-102 shares the core molecular structure of CUE-101, with primary differences in the tumor-specific T cell epitope. This similarity together with our preclinical data that demonstrated CUE-102’s ability to elicit selective expansion of WT1-specific T cells, support our belief for a potential positive tolerability profile and clinical activity. We look forward to sharing updated data on this trial in the coming year."

Key data highlights from CUE-102 preclinical study to date include:

CUE-102 selectively activated and expanded WT1-specific CD8+ T cells from peripheral blood mononuclear cells (PBMC) of healthy donors.
CUE-102 elicited and expanded WT1-specific CD8+ T cells from naïve mice without significantly altering the frequencies of other immune lineages.
The WT1-specific CD8+ T cells expanded in vivo exhibited polyfunctionality and selectively killed WT1-presenting target cells in vitro and in vivo.
All three posters will be available in the Investor & Media section of the Company’s website at www.cuebiopharma.com under Scientific Publications and Presentations.

SITC Presentation Details

Title: A phase 1 study of CUE-101, a novel HPV16 E7-pHLA-IL2-Fc fusion protein, as monotherapy and in combination with pembrolizumab in patients with recurrent/metastatic HPV16+ head and neck cancer
Abstract Number: 681
Presenter: Dr. Christine Chung, M.D., Chair, Department of Head and Neck-Endocrine Oncology, Moffitt Cancer Center, Tampa, Fla.
Date: Thursday, November 10, 2022, Poster Hall (Hall C) 9 a.m.–9 p.m. EST

Title: A phase 1, open-label, dose escalation and expansion study of CUE-102 monotherapy in HLA-A*0201 positive patients with WT1-positive recurrent/metastatic cancers
Abstract Number: 636
Presenter: Dr. Steven Margossian, M.D., Ph.D., Senior Medical Director at Cue Biopharma
Date: Friday, November 11, 2022, Poster Hall (Hall C) 9 a.m.–8:30 p.m. EST

Title: CUE-102 selectively activates and expands WT1-specific T cells for the treatment of patients with WT1+ malignancies
Abstract Number: 1323
Presenter: Dr. Natasha Girgis, Ph.D., Associate Director, Translational Pharmacology at Cue Biopharma
Date: Thursday, November 10, 2022, Poster Hall (Hall C) 9 a.m.–9 p.m. EST

About HPV+ Recurrent or Metastatic Head and Neck Cancer
Head and neck squamous cell carcinomas (HNSCC) are the 8th most common cancer in the world. A significant subset of the cases of HNSCC includes human papillomavirus (HPV) associated oropharyngeal tumors, with HPV16 detectable in 80%-90% of these cases. Despite the current standard of care treatments, more than 50% of patients with advanced HNSCC will experience recurrence, representing a significant unmet need.

About the CUE-100 Series
The CUE-100 series consists of Fc-fusion biologics that incorporate peptide-MHC (pMHC) molecules along with rationally engineered IL-2 molecules. This singular biologic is anticipated to selectively target, activate and expand a robust repertoire of tumor-specific T cells directly in the patient’s body. The binding affinity of IL-2 for its receptor has been deliberately attenuated to achieve preferential selective activation of tumor-specific effector T cells while reducing the potential for effects on regulatory T cells (Tregs) or broad systemic activation, potentially mitigating the dose-limiting toxicities associated with current IL-2-based therapies.

About SITC (Free SITC Whitepaper)
Established in 1984, the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) is a nonprofit organization of medical professionals dedicated to improving cancer patient outcomes by advancing the development, science and application of cancer immunotherapy and tumor immunology. SITC (Free SITC Whitepaper) is comprised of influential basic and translational scientists, practitioners, health care professionals, government leaders and industry professionals around the globe. Through educational initiatives that foster scientific exchange and collaboration among leaders in the field, SITC (Free SITC Whitepaper) aims to one day make the word "cure" a reality for cancer patients everywhere. Learn more about SITC (Free SITC Whitepaper) at sitcancer.org.

On November 10, 2022 Provectus (OTCQB: PVCT) reported that data from the Company’s ongoing, multi-cohort, Phase 1b/2 study of the combination therapy of cancer immunotherapy PV-10, an intratumoral formulation of Provectus’ small molecule rose bengal sodium (RBS), and immune checkpoint inhibitor KEYTRUDA (pembrolizumab) for the treatment of Stage III cutaneous melanoma will be presented at Melanoma Bridge 2022, to be held in Naples, Italy and online from December 1-3, 2022 (Press release, Provectus Biopharmaceuticals, NOV 10, 2022, View Source [SID1234623762]).

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The abstract accepted for video oral communication and poster presentation is entitled "Response for combination of PV-10 autolytic immunotherapy and immune checkpoint blockade in stage III cutaneous melanoma."

On November 10, 2022 Aptevo Therapeutics Inc. ("Aptevo" or the "Company") (NASDAQ:APVO), a clinical-stage biotechnology company focused on developing novel immuno-oncology therapeutics based on its proprietary ADAPTIR and ADAPTIR-FLEX platform technologies, reported financial results and business highlights for the quarter ended September 30, 2022 (Press release, Aptevo Therapeutics, NOV 10, 2022, View Source [SID1234623761]).

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Business Highlights

Presenting new Phase 1b expansion trial data for APVO436 in the treatment of Acute Myeloid Leukemia (AML) at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition being held December 10-13 in New Orleans, Louisiana
The poster, entitled "Updated Results from a Phase 1 Study of APVO436, a Novel Bispecific Anti-CD123 x Anti-CD3 ADAPTIR Molecule, in Relapsed/Refractory Acute Myeloid Leukemia and Myelodysplastic Syndrome"​ will be presented on Sunday, December 11, 2022 from 6:00 PM-8:00 PM Central time
Announced that the US Food and Drug Administration (FDA) issued a "may proceed" notification for the ALG.APV-527 investigational new drug application (IND), allowing the initiation of clinical trials evaluating the compound for the treatment of 5T4-expressing tumors in multiple solid tumor types
Continued dosing patients in the Company’s Phase 1b expansion program evaluating APVO436 for the treatment of acute myeloid leukemia in both combination therapy and monotherapy
"We are very excited to present our APVO436 expansion phase data at the upcoming ASH (Free ASH Whitepaper) meeting, fulfilling a promise we made earlier in the year and further underscoring our enthusiasm for the compound and rationale for its continued advancement in the clinic. We are also working to rapidly progress ALG.APV-527 in the clinic for evaluation in the treatment of solid tumors. Advancing our work across these programs will put us in a strong position to produce meaningful data readouts across our clinical programs in 2023," said Marvin White, President and CEO of Aptevo. Mr. White added "The combination of our existing cash and future expected milestone payments provides us sufficient runway to conduct our business for at least the next twelve months."

Third Quarter 2022 Financial Results Summary

Cash Position: Aptevo had cash, cash equivalents and restricted cash of $22.6 million as of September 30, 2022. This includes $0.4 million of restricted cash that was released in October 2022.

Royalty Revenue: For the three months ended September 30, 2022 and September 30, 2021, royalty revenue was $0 and $3.1 million, respectively. Royalty revenue for the period covered by this report reflects revenue recorded only in the first quarter of 2022 due to our Amendment to Royalty Purchase Agreement with HCR. As a result of the Amendment, we ceased reporting as royalty revenue royalties paid by Pfizer to HCR related to Pfizer’s sales of RUXIENCE (rituximab-pvvr). The last quarter for which we reported this royalty revenue was Q1 2022. The Amendment was effected to address a Nasdaq compliance matter and had the additional effect of eliminating the requirement to report all future Pfizer non-cash royalty revenue and extinguishing the liability that we recorded upon the initial sale of the royalties to HCR.

The Amendment does not affect the potential $22.5 million in milestone payments we may collect in the future based on achievement of RUXIENCE sales thresholds in 2022 and 2023 (up to $12.5 million related to 2022 sales and $10 million related to 2023 sales). RUXIENCE is a registered trademark of Pfizer.

Research and Development Expenses: For the three months ended September 30, 2022, research and development expenses increased by $0.1 million, to $4.5 million from $4.4 million for September 30, 2021. The increase is primarily due to higher spending on our APVO436 clinical trial as we continue to advance that trial in our Phase 1b expansion program.

General and Administrative Expenses: For the three months ended September 30, 2022, general and administrative expenses decreased by $0.2 million, to $3.3 million from $3.5 million for September 30, 2021. The decrease is primarily due to lower employee and consulting costs.

Other Income (Expense), Net: Other income (expense), net consists primarily of gain on extinguishment of liabilities, costs related to debt extinguishment, accrued exit fees on debt, non-cash interest on financing agreements, and interest on debt. Other expense, net was $0.3 million for the three months ended September 30, 2022, as compared to $2.3 million other expense, net for the three months ended September 30, 2021. The decrease is primarily due to no non-cash interest expense recorded during the period due to our Amendment to Royalty Purchase Agreement. Additionally, interest expense on our MidCap Credit Agreement has decreased due to principal payments made in 2022.

Discontinued Operations: For the three months ended September 30, 2022 and 2021, we collected $0.2 and $0.1 million in deferred payments from Medexus related to IXINITY sales, respectively. Pursuant to our LLC Purchase Agreement, the rate for deferred payments increased from 2% to 5% of net sales as of June 30, 2022.

Net Income (Loss): Aptevo’s net loss for the three months ended September 30, 2022, was $7.6 million or $1.50 per share, as compared to a net loss of $6.9 million or $1.43 per share for the corresponding period in 2021.

On November 10, 2022 Sapience Therapeutics, Inc., a clinical-stage biotechnology company focused on the discovery and development of peptide therapeutics to address oncogenic and immune dysregulation that drive cancer, reported the presentation of non-clinical and clinical data supporting the immune activating activity of ST101 at the SITC (Free SITC Whitepaper) 37th Annual Meeting in Boston, MA (Press release, Sapience Therapeutics, NOV 10, 2022, View Source [SID1234623760]). ST101 is a first-in-class antagonist of C/EBPβ, currently being evaluated in the Phase 2 portion of an ongoing Phase 1-2 clinical study in patients with advanced unresectable and metastatic solid tumors (NCT04478279).

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C/EBPβ is a leucine zipper family transcription factor that regulates macrophage differentiation, promoting the expression of M2 myeloid-derived suppressor cells (MDSCs) that contribute to suppression of antitumor immunity and correlate with poor prognosis. ST101 binds to C/EBPβ, preventing its dimerization and enhancing ubiquitin-proteasome dependent C/EBPβ degradation, resulting in repolarizing MDSCs from the immunosuppressive M2 to the pro-inflammatory M1 phenotype. In non-clinical studies, ST101 exposure to human peripheral blood mononuclear cells resulted in dose-dependent reduction in M2 macrophage and corresponding induction of pro-inflammatory M1 macrophage. At the highest ST101 concentration, a 40-fold increase in the M1/M2 ratio was observed. Validating these findings, subtherapeutic doses of ST101 significantly enhanced the anti-tumor activity of anti-PD1 antibodies in an orthotopic breast cancer tumor model. Sapience believes that reprogramming MDSCs from the M2 to the M1 phenotype represents a potential strategy to enhance antitumor immunity.

"These data validate the potential of ST101 to reprogram the tumor microenvironment to promote a more active immune system, which supports a novel, macrophage-driven mechanism of action for ST101," said Sapience CEO and President, Dr. Barry Kappel. "We are eager to broaden the development strategy of ST101 and explore combinations with immune-oncology molecules, such as checkpoint inhibitors, to treat solid tumor cancers with high unmet need."

"We are thrilled to present these data at SITC (Free SITC Whitepaper) 2022, the premier scientific meeting that showcases novel immunotherapy approaches for cancer," added Jim Rotolo, Ph.D., Sapience’s VP, Translational Pharmacology and Head of Research. "These data further elucidate the unique mechanism of action for ST101 and build upon our recent publication in Molecular Cancer Therapeutics, highlighting the therapeutic promise of disrupting C/EBPβ-driven oncogenic activity. We look forward to exploring the activity of ST101 in immune-oncology therapeutic strategies."

Further details of the ST101 mechanism of action can be found on the company’s website: ST101: Sapience Therapeutics, Inc.

SITC Poster Presentation Details:
Title: "ST101, a peptide antagonist of novel I/O target CEBPβ, reprograms MDSC polarization and decreases tumor-associated Tregs, suggesting an immune component to observed clinical responses"
Abstract Number: 1173
Location: Poster Hall C
Date/Time: Thursday, November 10, 2022 – Friday, November 11, 2022, 9am-9pm

The Sapience SITC (Free SITC Whitepaper) poster has been published as a supplement in the Journal for ImmunoTherapy of Cancer (JITC), the society’s global, open access, peer-reviewed journal, and is available on the Presentations section of the company’s website: Presentations :: Sapience Therapeutics, Inc.

About ST101
ST101, a first-in-class antagonist of C/EBPβ, is currently being evaluated in the Phase 2 portion of an ongoing Phase 1-2 clinical study in patients with advanced unresectable and metastatic solid tumors (NCT04478279). ST101-101 is an open-label, Phase 1-2 dose-finding study designed to determine the safety, tolerability, PK, PD, and proof-of-concept efficacy of ST101 in patients with advanced solid tumors. The study consists of two phases: Phase 1 dose escalation/regimen exploration and Phase 2 dose expansion. In the ongoing Phase 2 dose expansion, Sapience is actively enrolling patients with GBM, metastatic cutaneous melanoma, castration-resistant prostate cancer and locally advanced or metastatic hormone-receptor positive breast cancer. In the ongoing dose escalation part of the study, ST101 has demonstrated clinical proof-of-concept with a durable RECIST 1.1-confirmed partial response (PR) in a patient with cutaneous melanoma and evidence of long-lasting stable disease in several additional patients. In the ongoing Phase 2 dose expansion part of the study, ST101 has demonstrated clinical proof-of-concept with a mRANO-confirmed partial response in a patient with recurrent GBM and evidence of long-lasting stable disease in several additional patients.

ST101 has been granted Fast Track designation for recurrent GBM and advanced cutaneous melanoma in patients who have disease progression on or after anti-PD-1/anti-PD-L1 therapy, as well as orphan designations from the FDA for advanced melanoma, glioma and AML, and from the European Commission for the treatment of glioma.