On November 14, 2021 InnoCare Pharma (HKEX: 09969), a commercial-stage biotech company, reported the Investigational New Drug (IND) clearance of its SHP2 (Src Homology 2 domain containing protein tyrosine phosphatase) allosteric inhibitor ICP-189 by the US Food and Drug Administration (FDA) for starting clinical trial in the United States (Press release, InnoCare Pharma, NOV 14, 2021, View Source [SID1234595528]).

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This open, single-arm, multicenter study aims to evaluate the safety, tolerability, pharmacokinetics, and efficacy of ICP-189 as a monotherapy and combined treatment in patients with advanced solid tumors.

ICP-189 is being developed for the treatment of solid tumors as a single agent and/or in combinations with other antitumor agents.

Preclinical study shows that ICP-189 is a potent oral allosteric inhibitor of SHP2 with excellent selectivity over other phosphatases. SHP2 is a non-receptor protein tyrosine phosphatase involved in mediating MAPK signaling pathway and immune checkpoint pathway for the regulation of cellular proliferation and survival.

Dr. Jasmine Cui, Co-Founder, Chairwoman and CEO of InnoCare, said, "In less than a month after clinical approval of ICP-189 in China, our ICP-189 got clinical approval in the U.S. This is our fourth innovative drug entering clinical stage in the U.S. This year, our innovative drug candidates have been continuously recognized by the FDA: Orphan Drug Designation to pan-FGFR inhibitor gunagratinib for the treatment of cholangiocarcinoma; Breakthrough Therapy Designation to orelabrutinib for the treatment of relapsed or refractory mantle cell lymphoma; clinical approval of the second-generation pan-TRK inhibitor ICP-723… InnoCare will continue to innovate to meet the unmet clinical needs of the entire world. "

On November 14, 2021 Antengene Corporation Limited ("Antengene", SEHK: 6996.HK), a leading innovative global biopharmaceutical company dedicated to discovering, developing and commercializing first-in-class and/or best-in-class therapeutics in hematology and oncology, reported the presentation of three posters at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting in Washington D.C. (View Source) (Press release, Antengene, NOV 14, 2021, View Source [SID1234595529]).

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"Antengene is very pleased to present preclinical data on two of our Phase I programs, for ATG-101 and ATG-017, at the 2021 SITC (Free SITC Whitepaper) meeting on November 12, 2021. The unique mechanisms, promising preclinical safety and activity of these exciting new compounds are very much in keeping with Antengene’s mission to develop first-in-class, best-in-class medicines for cancer," said Jay Mei, M.D., Ph.D., Founder, Chairman and Chief Executive Officer of Antengene.

Dr. Mei continued, "These presentations also highlight the breadth and depth of Antengene’s drug development capabilities. The Antengene management team and I look forward to reviewing these posters, detailed below, and the Company’s exciting portfolio at our upcoming R&D Day, planned for November 16th (virtual, details below) and November 18th (in person, details below)."

Summary of Poster Presentations

Poster #893: ATG-101: Active in "Cold" tumors, No Preclinical Liver Toxicity

ATG-101 is a PD-L1 / 4-1BB bi-specific antibody that was designed to activate tumor infiltrating lymphocytes and inhibit immune checkpoints, without inducing liver toxicity. Antengene presented data from in vitro and in vivo studies that evaluated ATG-101 activity in several T-cell activation assays and multiple in vivo models, including those resistant to anti-PD(L)1 therapies.

Data in the poster showed that ATG-101 was active in anti-PD-L1 resistant and relapsed tumor models. In addition, ATG-101 increased the activation of T-cells and exhausted T-cells upon PD-L1 crosslinking (required for ATG-101 activity), rendering "cold" tumors "hot". Importantly, ATG-101 showed no liver toxicity in a GLP toxicity study (differentiating the drug vs other 4-1BB targeted monoclonals/bi-specifics) and did not induce cytokine release syndrome in an in vitro assay. ATG-101’s unique safety and efficacy properties make it a promising potential therapy for solid tumors and non-Hodgkins lymphoma.

Poster #608: Promising ATG-017 in vivo Combination Study Add to Clinical Strategy

ATG-017 is a potent small molecule kinase inhibitor targeting the extracellular signal-related kinases 1 and 2 (ERK1/2). Antengene presented data on an in vivo study that evaluated ATG-017 in combination with an anti-PD-L1 monoclonal antibody (atezolizumab), in an aggressive, immune checkpoint inhibitor resistant mouse cancer model.

Data in the poster showed that the combination enhanced the antitumor efficacy as well as increasing the percentage of infiltrating CD8+ T cells, NK cells, CD8:CD4 ratio and M1:M2 macrophage ratio in the tumor microenvironment, rendering a "cold" tumor "hot". These results demonstrated that ATG-017 has potential synergy with immune checkpoint inhibitors, providing a rationale for exploring combination therapy in the clinic in the pursuit of improved efficacy in solid tumors, including those resistant to checkpoint inhibitions.

Poster# 227: Computational Analysis Tool Enables ATG-101 Clinical Dose Selection

Bispecific antibody ATG-101 acts by forming a trimer (comprised of ATG-101 bound to PD-L1 and 4-1BB expressing cells) that activates tumor infiltrating lymphocytes and inhibits immune checkpoints. Measuring trimeric complexes is important in defining optimal clinical doses but is very challenging to do in the clinic.

Antengene and its collaborators at Applied BioMath, LLC reported on the development of a computational semi-mechanistic pharmacology model that could be used to define the clinical dose of ATG-101. It works by simulating in vivo tumor growth inhibition and predicting trimer formation, free drug levels and receptor occupancy over time. This work has enabled Antengene to define a clinically effective dose range of ATG-101 that induces >90% PD-L1 receptor occupancy, a key metric of drug activity. This valuable pharmacology tool, which may also be applied across other compounds in Antengene’s pipeline, reflects the Company’s enthusiasm to utilize novel technologies and partnerships to enhance drug development capabilities.

Details on the posters, published on the SITC (Free SITC Whitepaper) website, are shown below:

Abstract Number: 227
Title: A computational semi-mechanistic pharmacology model of ATG-101, a PD-L1/4-1BB bispecific antibody for treatment of solid tumors and NHL
Time: 7:00-17:00 EST, November 12-14, 2021
Presenter：Dr. David C. Flowers, Applied BioMath, LLC
First Author: Dr. David C. Flowers, Applied BioMath, LLC

Abstract Number: 608
Title: Synergistic effect of the combination of ATG-017, an ERK1/2 inhibitor, and immune checkpoint inhibitor in preclinical cancer models
Time: 7:00-17:00 EST, November 12-14, 2021
Presenter：Dr. Bing Hou, Antengene Corporation Limited
First Author: Dr. Peng Chen, Antengene Corporation Limited

Abstract Number: 893
Title: ATG-101, a novel PD-L1/4-1BB bispecific antibody, augments anti-tumor immunity through immune checkpoint inhibition and PDL1-directed 4-1BB activation
Time: 7:00-17:00 EST, November 12-14, 2021
Presenter：Dr. Bing Hou, Antengene Corporation Limited
First Author: Dr. Hui Yuwen, Antengene Corporation Limited

About ATG-101

ATG-101 is a novel PD-L1/4-1BB bi-specific antibody being developed for the treatment of multiple kinds of cancer. ATG-101 can activate anti-tumor immune effectors by simultaneously blocking the binding of PD-L1/PD-1 and inducing 4-1BB stimulation. In PD-L1 over-expressed cancer cells, ATG-101 has shown potent PD-L1 crosslinking-dependent 4-1BB agonist activity, thus potentially enhancing therapeutic efficacy, whilst mitigating risk of hepatoxicity. Antengene has received U.S. FDA approval for the IND for a Phase I trial of ATG-101 in solid tumors and non-Hodgkins lymphoma and is currently conducting a Phase I study of ATG-101 in Australia for the treatment of patients with metastatic/advanced solid tumors and non-Hodgkin lymphoma.

About ATG-017

ATG-017 is a potent and selective small molecule extracellular signal-regulated kinases 1 and 2 (ERK1/2) inhibitor. ERK1/2 are related protein-serine/threonine kinases that function as terminal kinases in the RAS-MAPK signal transduction cascade. This cascade regulates a large variety of cellular processes, including proliferation. The RAS-MAPK pathway is dysregulated in more than 30% of human cancers with the most frequent alterations being observed in RAS or BRAF genes across multiple tumor types. An ERK inhibitor enables the targeting of both RAS and BRAF mutant diseases. In nonclinical pharmacology studies, ATG-017 has demonstrated potent inhibition of ERK1/2 enzyme activity and tumor growth in vitro and in vivo. Antengene is conducting an open-label Phase I, dose-escalation study of ATG-017 in Australia for the treatment of patients with advanced solid tumors and hematologic malignancies.

About Antengene’s R&D Day

Antengene’s R&D Day will include presentations from Dr. Jay Mei, Founder, Chairman and CEO; Mr. John Chin, Chief Business Officer; Dr. Kevin Lynch, Chief Medical Officer; Dr. Bo Shan, Chief Scientific Officer, and other Company management.

The meetings will be held virtually in English on November 16, 2021, and on-site in Mandarin on November 18, 2021. A live webcast will be available on the Antengene website under "Investor Relations", on the Event Calendar page.

To attend the event, please register in advance at links below:

R&D Day English Session – Virtual Conference
Date: Tuesday, November 16, 2021
Time: 8:30 am – 11: 30 am, Eastern Time / 9:30 pm – 12: 30 am, Beijing Time
Register at: View Source
R&D Day Mandarin Session – Live Webcast of On-Site Meeting

Date: Thursday, November 18, 2021
Time: 1:30 pm – 5:30 pm, Beijing Time
Register at: View Source

On November 13, 2021 Compass Therapeutics, Inc. (Nasdaq: CMPX), a clinical-stage biopharmaceutical company developing proprietary antibody-based therapeutics to treat cancer, reported financial results for the third quarter ended September 30, 2021 and highlighted recent corporate accomplishments (Press release, Compass Therapeutics, NOV 13, 2021, View Source [SID1234595476]).

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"We have made major progress on reaching our corporate goals, highlighted by achieving significant advancements for both of our clinical stage programs and raising capital to support our objectives," said Thomas J. Schuetz, MD, PhD, Co-founder and Chief Executive Officer. "We released promising interim Phase 2a data on our lead program, CTX-009, which support our conviction that CTX-009 is a promising novel bispecific antibody therapy with activity across a broad range of solid tumors. Additionally, CTX-471 continues to advance well in development, and has demonstrated encouraging activity as a monotherapy in the post anti-PD-1/PD-L1 patient population, an area of a particularly high unmet medical need."

"On the financing side, we completed a $125 million public offering and concurrently uplisted to Nasdaq," added Vered Bisker-Leib, PhD, MBA, President and Chief Operating Officer. "We expect this offering will extend our cash runway into the fourth quarter of 2024, which will support the advancement of our pipeline. These are significant achievements for Compass and position us well to grow and fund key milestones throughout the next several years."

Third Quarter Development Highlights:

CTX-009 (DLL4 and VEGF-A bispecific antibody):

A Phase 2a study was initiated in Q1 2021 testing CTX-009 in combination with paclitaxel in patients with Biliary Tract Cancers (cholangiocarcinoma). Enrollment in the first part of the study has been completed and the criteria to advance to the second part of the study have been met. Notably, five partial responses (PRs) have already been observed among the first 17 patients evaluated leading to a preliminary overall response rate (ORR) of 29%, and all patients evaluated have had stable disease or better with a decline in tumor burden observed in 16 of the 17 patients leading to a Clinical Benefit Rate (CBR) of 100%. The study is being conducted in South Korea by Handok Pharmaceuticals and the clinicaltrials.gov identifier for the study is NCT04492033. Compass plans to submit an Investigational New Drug (IND) application to the Food and Drug Administration (FDA) in the fourth quarter of 2021 and subject to the IND clearance with the FDA, to initiate a Phase 2 study in 2022 in the United States.
CTX-471 (monoclonal antibody agonist of CD137, a key co-stimulatory receptor on immune cells):

We initiated a Phase 1b dose expansion study for CTX-471 in 2019 and treated 36 patients with 13 different tumor types in the study as of October 21, 2021. Of the 25 evaluable patients in the dose expansion part of the study, two patients had a PR, one of which has been confirmed by RECIST 1.1 and the other PR has been seen at the first tumor evaluation at Week 9. 11 patients have reached stable disease, leading to a preliminary ORR of 8% and a CBR of 52%. The first PR observed in the study was in a patient with advanced small cell lung cancer who had a PR at Week 17 and this response was confirmed at Week 25. This patient has now been treated with CTX-471 for more than one year with a durable PR. In October 2021, a second PR was observed in a patient with metastatic melanoma who was previously treated with and progressed on nivolumab. We expect to complete the Phase 1b stage of this study during the first half of 2022.
CTX-8371 (bispecific antibody that simultaneously targets both PD-1 and PD-L1):

We initiated IND-enabling studies and the GMP manufacturing campaign for CTX-8371. Due in part to delays at our contract development manufacturing organization, we are currently targeting an IND submission in the second half of 2022.
Third Quarter Corporate Highlights:

In November 2021, Compass closed an underwritten public offering to sell 35,715,000 shares of common stock at a public offering price of $3.50 per share. The gross proceeds to Compass from the offering, before deducting the underwriting discounts and commission, were approximately $125 million. In addition, the Company has granted the underwriters a 30-day option to purchase up to an additional 5,357,250 shares of common stock.
In connection with the public offering, Compass also uplisted its common stock to Nasdaq and its shares began trading on the Nasdaq Capital Market under the symbol "CMPX" on November 2, 2021.
Third Quarter 2021 Financial Results

Cash Position: As of September 30, 2021, cash and cash equivalents were $25.5 million as compared to $47.1 million as of December 31, 2020. The Company believes that our existing cash and cash equivalents, together with the proceeds of our November 2021 public offering, will allow us to fund our operating expenses and capital expenditures into the fourth quarter of 2024.
Research and development (R&D) Expenses: R&D expenses were $3.2 million for the third quarter of 2021, as compared to $3.7 million for the same period in 2020, a decrease of $0.5 million or 14%. The lower costs were principally driven by less depreciation expense of $0.3 million and program related expenses of $0.2 million.
General and Administrative (G&A) Expenses: G&A expenses were $2.7 million during the third quarter of 2021, as compared to $5.3 million for the same period in 2020, a decrease of $2.6 million or 49%. The lower costs were driven primarily by lower stock compensation expense of $1.4 million due to an accelerated vesting of shares and $0.5 million of professional fees related to the reverse merger in the third quarter of 2020. In addition, facilities expense decreased by $0.3 million.
Net Loss: Net loss for the third quarter was $6.0 million or $0.10 per diluted common share, compared to $9.2 million or $0.18 per diluted common share for the third quarter of 2020.

On November 13, 2021 Triumvira Immunologics ("Triumvira"), a clinical-stage company developing novel, targeted autologous and allogeneic T cell therapeutics that do not require gene editing and co-opt the natural biology of T cells to treat patients with solid tumors, reported the presentation of preclinical data from its proof-of-concept study in gastric cancer (Press release, Triumvira Immunologics, NOV 13, 2021, View Source [SID1234595519]). These new data demonstrate that Triumvira’s novel T cell antigen coupler (TAC)-T cell candidate targeting Claudin 18.2 (CLDN18.2) effectively eradicates CLDN18.2-expressing gastric tumor cells in vitro and in vivo. The results will be presented in a poster presentation today at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 36th Annual Meeting, taking place November 10-14, 2021, virtually and in-person at the Walter E. Washington Convention Center in Washington, D.C.

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CLDN18.2 is a promising, clinically validated target for cancer drug development as gastrointestinal malignancies, more prominently gastric tumor cells, have been found to selectively express CLDN18.2 on their surface, making it a preferred antigen for specific targeting of tumor cells using TAC-T cells. A key feature of TAC-T cells is the proprietary TAC receptor, a multi-domain chimeric molecule that works directly with the natural T cell receptor to help a T cell recognize and attack cancer cells. Unlike CAR-T cells, TAC-T cells do not exhibit tonic signaling, do not show premature exhaustion, show long term persistence, and demonstrate deep penetration into and activation in solid tumors in various preclinical models.

"We’re excited about the level of activity we are seeing with our Claudin 18.2-directed TAC-T cells in our preclinical models of gastric cancer," said Andreas Bader, Ph.D., Chief Scientific Officer of Triumvira. "These results confirm the versatility of our TAC platform for difficult-to-treat solid tumors and pave the way for initiating IND-enabling studies in an effort to bring CLDN18.2-TAC T cells to patients as quickly as possible in an area of significantly unmet medical need."

In addition to eradicating CLDN18.2-expressing gastric tumor cells in vitro and in vivo, the study demonstrated that the activation of CLDN18.2-TAC T cells was specific to target cells that expressed CLDN18.2. CLDN18.2-TAC T cells did not show signs of auto-activation or elevated exhaustion markers post-manufacturing, which is a key feature of the TAC technology designed to enhance the durability of TAC-T products.

Details of the poster presentation are as follows:

Poster Title: Development of Claudin 18.2 TAC T cells for the treatment of gastric cancer
Poster Number: 118
Category: Cellular Therapies
Date and Time: Saturday, November 13, 2021; 7:00 a.m. – 8:30 p.m. EST
Location: Walter E. Washington Convention Center, Hall E
Presenter: Christopher Helsen, Ph.D. – Executive Director, Research and Development, Triumvira

On November 13, 2021 Seven and Eight Biopharmaceuticals Inc., a clinical stage biotechnology company developing proprietary novel immuno-oncology therapies to activate the immune system against cancer, reported the presentation of interim Phase 1 data for BDB001 in combination with atezolizumab in advanced solid tumors at the 2021 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting (Press release, Seven and Eight Biopharmaceuticals, NOV 13, 2021, View Source [SID1234595520]).

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BDB001 is an immune modulator capable of activating dendritic cells to initiate both innate and adaptive immunity against cancer. BDB001 is a first-in-class TLR7/8 agonist delivered intravenously, allowing for broader treatment of solid tumors. Previously, Seven and Eight Biopharma reported that intravenous administration of BDB001 both as monotherapy and in combination with an anti-PD-1 mAb exhibit favorable tolerability and robust systemic immune activation leading to durable clinical responses in multiple advanced solid tumor types (SITC, 20201; ASCO (Free ASCO Whitepaper), 20212).

The presentation at SITC (Free SITC Whitepaper) 2021 provides interim safety and efficacy results for a Phase 1 dose escalation / expansion trial of BDB001 in combination with atezolizumab in advanced solid tumors (NCT04196530). The results show that BDB001 in combination with atezolizumab is well tolerated with evidence of robust immune activation leading to clinical responses in multiple tumor types.

"It is encouraging to see that BDB001 in combination with atezolizumab can be safely delivered intravenously and produces clinical responses in heavily pre-treated tumors" said lead author and study investigator Dr. Manish R. Patel, of Florida Cancer Specialists/Sarah Cannon Research Institute.

"These promising interim results show that BDB001 in combination with atezolizumab represents a novel and viable treatment for advanced solid tumors. It is especially encouraging to see responses in both PD-1 naïve and refractory tumors." said Dr. Robert H.I. Andtbacka, Chief Medical Officer, Seven and Eight Biopharma. "The Phase 1 trial helped establish the BDB001 phase 2 dose which is being evaluated in an ongoing Phase 2 trial (NCT03915678) of BDB001 in combination with atezolizumab and radiotherapy in selected tumor types."

"We are very excited about the clinical data for BDB001 in combination with atezolizumab, as we continue to advance our robust immuno-oncology pipeline in treatments beyond anti-PD-(L)1, including preclinical platform programs in TLR Ligand Antibody Conjugation" said Dr. Walter Lau, Chief Executive Officer, Seven and Eight Biopharma.

Presentation Details:

Abstract Title: BDB001, a Toll-Like Receptor 7 and 8 (TLR7/8) agonist, can be safely administered intravenously in combination with atezolizumab and shows clinical responses in advanced solid tumors.

Abstract Authors: Manish R. Patel, Drew W. Rasco, Melissa L Johnson, Anthony W. Tolcher, Angela Tatiana Alistar, David Sommerhalder, Omid Hamid, Lixin Li, Alexander H. Chung, Robert H.I. Andtbacka

Session: Poster Presentation

On-Demand Session Release Date and Time: November 13th, 2021 @ 7:00 AM

Abstract Number: 472

The poster presentation will be available at the SITC (Free SITC Whitepaper) 2021 Annual Meeting website.

Abstract Summary:

Seven and Eight Biopharma’s systemic delivery of the TLR 7 and 8 dual agonist BDB001 is first in class.
BDB001 was delivered safely intravenously in combination with atezolizumab.
BDB001 in combination with atezolizumab showed robust dose dependent immune activation without increased risk of cytokine release syndrome.
Overall, BDB001 was well tolerated and 31.7% of subjects did not have any treatment related adverse events. No DLTs occurred and there were no Grade 4 or 5 Adverse Events.
Clinical responses were seen in subjects with urothelial carcinoma and non-small cell lung cancer and showed evidence of robust anti-tumor immune activation.
Clinical responses were seen in tumors that had progressed on anti-PD-1 therapy and with low probability of responding to anti-PD-(L)1 therapy based on their PD-L1 negative, MSI-stable, and Tumor Mutational Burden-low status.
A Phase 2 trial has been initiated and is actively enrolling subjects to further investigate BDB001 in combination with atezolizumab and radiotherapy in patients with advanced solid tumors
BDB001 in combination with atezolizumab represents a novel and viable therapeutic option for patients with advanced solid tumors.