On November 12, 2021 Monopar Therapeutics Inc. (Monopar or the Company) (Nasdaq: MNPR), a clinical-stage biopharmaceutical company focused on developing proprietary therapeutics designed to extend life or improve the quality of life for cancer patients, reported third quarter 2021 financial results and summarized recent clinical developments (Press release, Monopar Therapeutics, NOV 12, 2021, View Source [SID1234595449]).

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Recent Clinical Developments

Validive

Monopar received clearance in multiple European countries to conduct its Phase 2b/3 VOICE clinical trial of Validive (clonidine HCl mucobuccal tablet) for the prevention of severe oral mucositis (SOM) in patients undergoing chemoradiotherapy (CRT) for oropharyngeal cancer.
Monopar continues to actively initiate additional clinical sites in both the U.S. and the EU for the Phase 2b clinical trial, which is on track to reach the interim in the first half of 2022.
There remains no FDA-approved prevention or treatment for CRT-induced SOM.
Camsirubicin

Camsirubicin, a propriety doxorubicin analog, has been engineered specifically to retain the anticancer activity of doxorubicin while minimizing the toxic effects on the heart.
In August 2021, Monopar received clearance from the U.S. Food and Drug Administration to proceed under an Investigational New Drug (IND) application with an open-label Phase 1b dose-escalation clinical trial evaluating camsirubicin plus growth factor support (pegfilgrastim/G-CSF) in patients with advanced soft tissue sarcoma.
In September 2021, Monopar initiated the Phase 1b clinical trial, and in October 2021, dosed the first patients.
Monopar continues to work on activating additional clinical sites in the U.S. for the Phase 1b clinical trial.
Results for the Third Quarter Ended September 30, 2021, Compared to the Third Quarter Ended September 30, 2020

Cash and Net Loss

Cash and cash equivalents as of September 30, 2021, were $22.3 million. Monopar anticipates that its current cash and cash equivalents will fund: the Phase 2b portion of the VOICE clinical trial; the commencement of the Phase 3 portion of the VOICE clinical trial; and the Phase 1b camsirubicin clinical trial through December 2022. The Company plans to raise additional funds and/or engage a partner within the next 12 months to complete the VOICE clinical program and continue camsirubicin clinical development beyond the Phase 1b clinical trial.

Net loss for the third quarter of 2021 was $2.5 million or $0.20 per share compared to net loss of $1.6 million or $0.15 per share for the third quarter of 2020.

Research and Development (R&D) Expenses

R&D expenses for the third quarter of 2021 were $1.8 million compared to $1.2 million for the third quarter of 2020. This increase of $0.6 million was primarily due to increases of $0.5 million for VOICE clinical trial expenses and $0.2 million for R&D personnel expenses offset by a decrease of $0.1 million for Phase 1b camsirubicin clinical trial expenses.

General and Administrative (G&A) Expenses

G&A expenses for the third quarter of 2021 were $0.6 million, compared to $0.4 million for the third quarter of 2020. This increase of $0.2 million was primarily due to an increase in G&A personnel expenses.

On November 12, 2021 Celyad Oncology SA (Euronext & Nasdaq: CYAD), a clinical-stage biotechnology company focused on the discovery and development of chimeric antigen receptor T cell (CAR T) therapies for cancer, reported three poster presentations on the Company’s allogeneic CAR T therapy programs at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting taking place in Washington D.C. and virtually November 10-14, 2021 (Press release, Celyad, NOV 12, 2021, View Source [SID1234595448]).

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"With these presentations, we demonstrate how we continue to execute on our strategic vision to develop differentiated next generation CAR Ts using our non-gene edited allogeneic approaches which are intended to provide multiple real-world benefits to patients," said David Gilham, Ph.D., Chief Scientific Officer of Celyad Oncology. "We believe our CAR T cells are the only allogeneic CAR T cells currently in human clinical trials that avoid generating double-strand DNA breaks. Combining with multiplexed shRNA and cytokine armoring, we believe this approach provides us with a dynamic platform for the generation of future allogeneic candidates."

Charles Morris, M.D., Chief Medical Officer of Celyad Oncology said, "In addition to the encouraging preclincal data presented, we are also on the cusp of initiating the KEYNOTE-B79 Phase 1b clinical trial in collaboration with MSD. We believe that KEYNOTE-B79 will be the first clinical trial to evaluate an allogeneic CAR T with an anti-PD-1 therapy in solid tumors. We look forward to evaluating whether the expected highly complementary mechanism of actions of CYAD-101 and KEYTRUDA could help to drive important clinical benefit in patients with refractory metastatic colorectal cancer with microsatellite stable disease where a high unmet medical need exists. We look forward to initiating the study in the coming weeks and providing clinical updates to the CYAD-101 program in 2022."

Key Highlights from SITC (Free SITC Whitepaper) Annual Meeting

Poster 107 – Armoring NKG2D CAR T cells with IL-18 improves in vitro and in vivo anti-tumor activity

This poster demonstrates the key role of Interleukin-18 (IL-18) in driving increased effector function of the NKG2D CAR T cells.
These data support the ongoing development of the Company’s shRNA-based allogeneic, IL-18-armored CAR T candidate CYAD-203 as well as future allogeneic IL-18-armored CAR T candidates.
Poster 146 – Evolving multiplexed shRNA to generate tailored CAR T cell therapy

Multiplexing short hairpin RNA (shRNA) within a single vector format ensures co-linked expression of the shRNA with therapeutic transgenes.
We continue to develop second-generation shRNA scaffold using multiplexed technology to produce novel allogeneic clinical candidates with bespoke, desired phenotypes and function produced using methods that avoid the generation of double strand DNA breaks.
Poster 407 – A Phase 1b KEYNOTE-B79 trial evaluating non-gene edited allogeneic CAR T-cells, CYAD-101, post FOLFOX preconditioning, followed by pembrolizumab, in refractory metastatic colorectal cancer patients

Clinical and translational results from the alloSHRINK Phase 1 trial evaluating the TCR Inhibitory Molecule (TIM)-based allogeneic NKG2D CAR T-cell product candidate CYAD-101 (NCT03692429) in patients with metastatic colorectal (mCRC) cancer suggest that treatment with sequential checkpoint inhibition following CYAD-101 with FOLFOX preconditioning could drive more durable clinical responses.
The KEYNOTE-B79 trial will therefore evaluate the safety and clinical activity of multiple infusions of CYAD-101 administered post FOLFOX preconditioning chemotherapy, followed by treatment with KEYTRUDA (pembrolizumab) in mCRC patients with microsatellite stable disease, according to a Simon’s two stage trial design.
The KEYNOTE-B79 clinical trial is expected to begin in fourth quarter 2021.
These ePosters will be available on the SITC (Free SITC Whitepaper) website starting today at 1 p.m. CET / 7 a.m. ET and in the Scientific Publications section of Celyad Oncology’s website.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

On November 12, 2021 Neoleukin Therapeutics, Inc., "Neoleukin" (NASDAQ:NLTX), a biopharmaceutical company utilizing sophisticated computational methods to design de novo protein therapeutics, reported the presentation of new preclinical data on NL-201, an alpha-independent, de novo-designed IL-2 and IL-15 dual agonist, at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s 36TH Annual Meeting (SITC 2021) (Press release, Neoleukin Therapeutics, NOV 12, 2021, View Source [SID1234595447]).

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The presentation highlights preclinical data on NL-201 alone and in several combination regimens. NL-201 is a de novo agonist of the IL-2 and IL-15 receptors, designed to expand cancer-fighting CD8 T cells and natural killer (NK) cells without any bias toward cells expressing the IL-2 receptor alpha subunit (CD25).

"The SITC (Free SITC Whitepaper) presentations highlight the broad potential of NL-201, which we believe to be the first fully de novo designed protein to enter clinical trials, to activate the immune system to fight cancer," said Jonathan Drachman, M.D., Chief Executive Officer of Neoleukin. "New data demonstrate that NL-201 can activate the tumor microenvironment and increase T-cell receptor diversity. We also found that local, intratumoral administration can control both the injected and distant tumors with improved tolerability compared to systemic administration in pre-clinical models. We are pleased to share this research as we continue to advance the NL-201 phase 1 clinical trial."

Further details from the presentations are as follows:

Poster/Abstract Number: 716
NL-201 Induces Inflammation in a ‘Cold’ Tumor Microenvironment through Upregulation of MHC-I, Expansion of the TCR Repertoire, and Potent Antitumor Activity when Combined with PD-1 Inhibition

NL-201 turns "cold" tumors "hot" by increasing pro-inflammatory T cells and an immune signature in the tumor microenvironment and upregulating MHC-1 in tumors.
NL-201 stimulates pro-inflammatory tumor reprogramming without the coincident Treg expansion observed with PD-1 antibodies and other immuno-oncology agents.
NL-201 drives anti-tumor efficacy in a manner that is cooperative with PD-1 inhibition, including increasing TCR repertoire diversity.
Poster/Abstract Number: 898
Intratumoral Administration of NL-201, an Alpha-Independent IL-2/15 Receptor Agonist, Inhibits the Growth of Both Injected and Uninjected Tumors in Preclinical Models

Intratumoral NL-201 administration demonstrated:
Dose-dependent antitumor activity in syngeneic murine tumor models;_
Improved tolerability compared to systemic administration at equivalent dose levels and;
Durable tumor-specific immunity.
Results support clinical investigation of intratumoral NL-201 administration to increase NL-201 concentration in accessible lesions and reduce systemic exposure.
Poster/Abstract Number: 509
A First-in-Human Phase 1 Study of NL-201 in Patients with Relapsed or Refractory Cancer (Trials in Progress)

Assessing the safety profile and recommended Phase 2 dose and treatment schedule of NL-201.
Dose escalation and dose expansion cohorts.
Enrollment ongoing at multiple sites in North America and Australia.
Poster/Abstract Number: 563
ICT01, an Anti-BTN3A Monoclonal Antibody, and NL-201, an Alpha-Independent IL-2/IL-15 Agonist, Combine to Elicit a Potent Anti-Tumor Response by Synergistically Stimulating g9d2 T Cell Activation and Proliferation

ICT01 plus NL-201 synergistically triggers gd T-cell activation, expansion and antitumor activity.
Data support clinical evaluation of this novel therapeutic approach.
The poster presentations are available on the Neoleukin website publications page: View Source

About NL-201
NL-201 is a de novo agonist of the IL-2 and IL-15 receptors, designed to expand cancer-fighting CD8 T cells and natural killer (NK) cells without any bias toward cells expressing the alpha receptor subunit (CD25). Previously presented preclinical data has demonstrated the ability of NL-201 to stimulate and expand CD8+ and NK cells at low doses with minimal impact on immunosuppressive regulatory T cells. Furthermore, NL-201 has demonstrated both monotherapy and combination activity across a wide range of preclinical syngeneic tumor models.

On November 12, 2021 Can-Fite BioPharma Ltd. (NYSE American: CANF) (TASE: CFBI), a biotechnology company advancing a pipeline of proprietary small molecule drugs that address inflammatory, cancer and liver diseases, reported the Company’s CEO Dr. Pnina Fishman will present at the H.C. Wainwright 7th Annual Israel Conference on Monday, November 15, 2021 at 12:30 PM ET (Press release, Can-Fite BioPharma, NOV 12, 2021, View Source [SID1234595446]). In addition to the presentation, management will conduct one-on-one meetings with investors at the virtual conference.

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Dr. Fishman will highlight Can-Fite’s advanced stage pipeline including a completed Phase III study in psoriasis with data anticipated in Q1 2022 and upcoming studies that are expected to commence enrollment including a Phase II study in NASH and a pivotal Phase III in liver cancer.

On November 12, 2021 Checkmate Pharmaceuticals, Inc. (NASDAQ: CMPI) ("Checkmate"), a clinical stage biotechnology company focused on developing proprietary technology to harness the power of the immune system to combat cancer, reported the presentation of final clinical data from the Phase 1b study, CMP-001-001 (NCT02680184), of vidutolimod, an advanced generation Toll-like receptor 9 (TLR9) agonist, in combination with pembrolizumab or as a monotherapy at The Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 36th Annual Meeting taking place on November 10-14, 2021 (Press release, Checkmate Pharmaceuticals, NOV 12, 2021, View Source [SID1234595445]).

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"Our ongoing investigation of vidutolimod indicates promising clinical activity for patients with PD-1 blockade-refractory melanoma," said Alan Fuhrman, interim President and Chief Executive Officer of Checkmate. Mr. Fuhrman added, "The RECIST response rates of 20% with vidutolimod monotherapy and 23.5% in combination with pembrolizumab are compelling, and the longer duration of response of 25.2 months in combination with PD-1 blockade provides a strong rationale for our ongoing development program."

Final analysis: phase 1b study investigating intratumoral injection of Toll-like receptor 9 agonist vidutolimod ± pembrolizumab in patients with PD-1 blockade–refractory melanoma (Abstract #16269; poster #950; NCT02680184)

On Friday, November 12, 2021, during the Virtual Poster Hall Exhibit from 7:00am – 8:30pm ET, John M. Kirkwood, M.D., Director of the Melanoma and Skin Center at UPMC Hillman Cancer Center and Usher Professor of Medicine in the Division of Dermatology and Translational Science at the University of Pittsburgh School of Medicine, is presenting late-breaking final clinical data from the Checkmate-sponsored clinical trial of vidutolimod, either in combination with pembrolizumab or as monotherapy.

Final clinical data from the trial demonstrated that the combination of vidutolimod and pembrolizumab was well tolerated and resulted in an ORR of 23.5% according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. The study treatment induced deep and durable systemic antitumor responses in patients with melanoma who previously progressed on anti-PD-1 treatments.

"PD-1 blockade therapy has significantly improved clinical outcomes for many patients with cancer, although most patients still experience disease progression on anti−PD-1-therapy. Therapeutic alternatives for these patients are a large gap in the field, and critically needed," said Dr. Kirkwood. "With clinically meaningful tumor regression we have observed both in injected and noninjected lesions, vidutolimod’s systemic effects hold the potential to enhance responsiveness and overcome resistance to immune checkpoint inhibitors. In addition, the substantially improved duration of response with the combination of vidutolimod and anti-PD-1 therapy provides strong rationale for further development of vidutolimod in combination with PD-1 blockade."

Data were presented on 159 patients receiving combination therapy with vidutolimod and pembrolizumab. Two formulations of vidutolimod were evaluated, either polysorbate 20 at 0.01% (PS20, n=98) or x PS20 at 0.00167% (n=61). Based on the results, vidutolimod PS20 A 10 mg (schedule A) was selected as the Recommended Phase 2 Dose (RP2D) and schedule. Data were also presented on 40 patients who received vidutolimod monotherapy.

Key highlights from these clinical data as of the data cut-off of August 17, 2021 include:

Vidutolimod in combination with pembrolizumab

The best ORR by RECIST v1.1 in patients who received vidutolimod PS20 A+ pembrolizumab was 23.5% (95% CI 15.5-33.1), including 7.1% (7/98) of patients with a complete response.
Four additional patients who continued study therapy beyond initial disease progression achieved a partial response.
Vidutolimod PS20 A 10 mg (schedule A) was selected as the RP2D.
The Kaplan-Meier estimate for median duration of response was 25.2 months (95% CI8.7- not estimable [NE] in the 23 RECIST v1.1 responders).
Among responding patients, non-injected target lesions regressed by a similar magnitude to injected target lesions.
The most common treatment-related adverse events were chills, pyrexia, fatigue, nausea, vomiting and injection site pain.
Vidutolimod as a monotherapy

In the 40 patients who received vidutolimod monotherapy, the best ORR by RECIST v1.1 was 20.0% (95% CI, 9.1-35.6).
The median duration of response was 5.6 months (95% CI, 3.1-NE).
The most common treatment-related adverse events were chills, pyrexia, nausea, fatigue, headache, hypotension, and pruritus.