On November 15, 2021 Redx Pharma (AIM: REDX), the clinical-stage biotechnology company focused on discovering and developing novel, small molecule, highly targeted therapeutics for the treatment of cancer and fibrotic disease, reported that the first patient has been dosed in the monotherapy arm of the Phase 2 clinical trial of its investigational drug RXC004 in patients with advanced microsatellite stable (MSS) metastatic colorectal cancer (mCRC) who have progressed following treatment with standard of care (Press release, Redx Pharma, NOV 15, 2021, View Source [SID1234595549]). RXC004 is Redx’s wholly-owned, highly potent and selective, orally active once-daily Porcupine inhibitor being developed as a targeted therapy for Wnt-ligand driven cancer.

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 multi-centre Phase 2 clinical trial (clinicaltrials.gov NCT04907539) will evaluate preliminary efficacy and safety of RXC004 in genetically-selected patients with Ring finger protein 43 (RNF43) or R-spondin (RSPO) aberrated, advanced MSS mCRC. Topline data is expected to report in the first half of 2023.

A second arm of the trial, evaluating RXC004 in combination with the anti-PD-1 antibody nivolumab in patients with MSS mCRC, is expected to commence in the first half of 2022 once a recommended dose has been established in the ongoing Phase 1 dose escalation combination trial.

D r Natalie Cook, University of Manchester and Christie NHS Foundation Trust, UK, and International Coordinating Investigator of the study in the UK, commented: "Microsatellite stable metastatic colorectal cancer is a devastating disease, with limited treatment options. A subgroup of these colorectal cancers possess RNF43 mutations or RSPO fusions leading to activation of the Wnt pathway as a driver of the cancer. This study will assess whether RXC004, a novel Porcupine inhibitor, has a clinically meaningful anti-cancer effect in this well-defined patient cohort.”

Lisa Anson, Chief Executive Officer of Redx Pharma, added: "We are excited to be dosing patients in Redx’s first ever Phase 2 clinical trial of a wholly-owned drug candidate, an important corporate milestone. Our encouraging Phase 1 results, recently reported at the ESMO (Free ESMO Whitepaper) Congress, combined with our preclinical data, strongly support the hypothesis that patients with Wnt-ligand driven tumours could benefit from RXC004."

A second Phase 2 clinical trial evaluating RXC004 as a monotherapy in advanced genetically selected pancreatic cancer and unselected biliary cancer is also expected to start in 2021.

About microsatellite stable metastatic colorectal cancer (MSS mCRC)
Metastatic colorectal cancers have a poor prognosis with a 5-year survival rate of approximately 15% (1). Standard first line and second line treatments are combinations of chemotherapy and a VEGF inhibitor or EGFR inhibitor. MSS cancers account for 95% of metastatic CRC and tend to be unresponsive to treatment with immune checkpoint inhibitors. In the third line treatment setting the response rate to standard agents is <5%, median progression free survival is approximately 2 months and overall survival approximately 6 months (2,3). Approximately 8% of MSS mCRC patients have Wnt-ligand driven tumours (3% RNF43 mutations and 5% RSPO fusions) (4)

About RXC004
RXC004 is a wholly owned, potent, selective, oral, small-molecule inhibitor of the Porcupine enzyme, a key activator of Wnt ligands in the Wnt-signalling pathway. The Wnt pathway is well established as a driver of both tumour growth and immune evasion. Aberrant Wnt signalling contributes directly to tumour growth and plays an important role in immune evasion, which has also been linked to resistance to immune-checkpoint inhibitors (ICIs) such as nivolumab. By selecting patients with tumours that have high Wnt-ligand dependency, such as those with loss of function mutations in the RNF43 gene and fusions in the RSPO gene family, RXC004 has an opportunity to both directly inhibit the tumour growth and have an immune-enhancing effect to allow the patient’s immune system to better recognise and attack the tumour.

ICIs such as anti-PD-1 antibodies have revolutionised the treatment of cancer, but do not work in all patients. Wnt-pathway activation can enhance the ability of the tumour to evade destruction by the immune system and has been linked to lack of response to ICIs in these tumours. Redx scientists have observed in preclinical studies that RXC004 can block activation of the Wnt pathway and restore the ability of the immune system to fight the tumour. Thus, RXC004 offers potential to address some of the shortcomings of ICI therapies through increasing both response rates and duration of response, particularly in patient populations unresponsive to ICI therapy.

On November 15, 2021 T-knife Therapeutics, Inc., a biopharmaceutical company dedicated to developing novel therapeutics to fight cancer, reported preclinical data demonstrating that its novel MAGE-A1-specific T cell receptor (TCR) induced meaningful anti-tumor activity and enhanced engraftment as compared to human donor derived TCRs (Press release, T-Knife, NOV 15, 2021, View Source [SID1234595592]). In vivo data presented at the SITC (Free SITC Whitepaper) annual meeting highlight the potential of T-knife’s lead product candidate TK-8001, a TCR engineered T cell therapy (TCR-T) that is being developed to treat MAGE-A1 positive solid tumors. The company plans to initiate a first-in-human, Phase 1/2 trial in early 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!

T-knife has used its proprietary HuTCR platform to discover multiple naturally optimized high-affinity TCRs specific for the cancer-testis antigen MAGE-A1. These MAGE-A1-specific TCRs were isolated from the HuTCR platform and in vitro and in vivo activity were compared to different human-derived MAGE-A1-specific TCRs. T-knife’s TCRs, including the TCR incorporated in TK-8001, were found to be of higher affinity than human derived TCRs and resulted in superior anti-tumor activity, as shown in a syngeneic preclinical model. In addition, TK-8001 exhibited enhanced engraftment rates, as measured by TCR+ cells in peripheral blood. The data generated in these preclinical evaluations highlight the potential therapeutic benefit of TK-8001.

In a separate trial-in-progress poster at the conference, the company provided detail on its planned IMAG1NE Phase 1/2 trial of TK-8001 to evaluate the safety, tolerability, and clinical activity of TK-8001 in advanced-stage, metastatic, MAGE-A1 positive solid tumors. The trial will be conducted in two phases, including a dose escalation phase designed to select the optimal dose to be utilized in a subsequent open-label expansion cohort. A supporting translational poster validating MAGE-A1 as an attractive solid tumor target was also presented.

"It is gratifying for our R&D team to present this exciting preclinical efficacy data in solid tumors expressing MAGE-A1," said Elisa Kieback, Ph.D., founder and Chief Technical Officer of T-knife Therapeutics. "Advancing this program toward the clinic and clinical proof of concept for our TCR platform is an important corporate milestone and highlights the substantial progress we have been making over the past year. We look forward to generating clinical data with TK-8001 with the initiation of our IMAG1NE Phase 1/2 study in select patients with MAGE-A1 expressing solid tumors.

About TK-8001 TCR-T

TK-8001 is a CD8 TCR-T specific for the Melanoma-associated Antigen Gene-A1, or MAGE-A1. MAGE-A1 is associated with hallmarks of aggressive cancers and poor clinical prognosis, and there is an emerging body of evidence indicating its involvement as a potential driver of tumorigenesis. MAGE-A1 represents an attractive therapeutic target given the high unmet need in MAGE-A1 expressing cancers, no reported protein expression in healthy tissues other than testis and significant consistency of expression between the primary tumor and metastases. As high affinity TCRs specific for MAGE-A1 peptides in humans are eliminated through central tolerance, we believe our HuTCR platform is a differentiated means to discover and select MAGE-A1 specific TCRs with an optimal affinity and high specificity profile.

About the IMAG1NE Phase 1/2 Trial

The IMAG1NE Phase 1/2 trial is an open-label, multi-center Phase 1/2 trial designed to evaluate the safety and efficacy of TK-8001 in patients with MAGE-A1 positive solid tumors. The first phase of the IMAG1NE trial is planned to enroll approximately 6 to 18 patients to assess the initial safety and tolerability of ascending dose levels of TK-8001. A key outcome of the first phase of the trial is to select a dose to be evaluated in an open label expansion phase of the study. The open label expansion phase of the IMAG1NE trial is designed to enroll approximately 30 additional participants to assess the efficacy of TK-8001 across a range of tumor indications

On November 15, 2021 Inhibikase Therapeutics, Inc. (Nasdaq: IKT) (Inhibikase), a clinical-stage pharmaceutical company developing therapeutics to modify the course of Parkinson’s disease and related disorders, reported financial results for the third quarter ended September 30, 2021 and highlighted recent developments (Press release, Inhibikase Therapeutics, NOV 15, 2021, View Source [SID1234595608]).

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!

Key Business and Clinical Highlights

Dosed first patient in the Phase 1b clinical trial of IkT-148009: In October 2021 Inhibikase dosed the first patient in its Phase 1b clinical trial of IkT-148009, a randomized, placebo-controlled trial to evaluate the safety, tolerability, and pharmacokinetics of IkT-148009. The trial will enroll a total of 24 patients with Parkinson’s disease and also assess non-motor and motor function, gut motility, and measures of alpha-synuclein aggregate clearance, as exploratory endpoints. The Company expects to complete this study and, with the approval of the U.S. Food and Drug Administration (FDA), advance into a Phase 2a study in 2022.
Extended Phase 1 clinical trial of IkT-148009 to higher doses: In October 2021, Inhibikase expanded dosing of IkT-148009 in older and elderly healthy volunteers up to a single 250 mg dose to identify the maximum tolerated dose. This extension was based on the safety and tolerability profile observed in the initial dose cohorts of the Phase 1 study.
Submitted interim three-month results from chronic toxicology studies of IkT-148009 to FDA: In October 2021, Inhibikase reported that it had submitted interim three-month results from its ongoing chronic toxicology studies of IkT-148009 in rats and non-human primates to the FDA. Data indicated that the toxicology profile of IkT-148009 improves with extended daily oral dosing and supports evaluation in Parkinson’s patients for up to three months.
Received grant from U.S. National Institutes of Health to evaluate IkT-148009 for the treatment of Multiple System Atrophy: In September 2021, Inhibikase was awarded a research grant from the U.S. National Institute of Neurological Disease and Stroke (NINDS), an Institute of the National Institutes of Health (NIH), to evaluate the mechanism of the MSA disease process and the therapeutic potential of IkT-148009 in preclinical studies.
"Over the past quarter, we have worked diligently to advance our lead candidate, IkT-148009 in multiple indications. We dosed the first Parkinson’s patient in our Phase 1b study as well as submitted interim chronic toxicology data to the FDA to support extended dosing of IkT-148009. We were also pleased to receive a grant from the NIH to evaluate IkT-148009 in a novel preclinical model of MSA, a neurodegenerative disease that may benefit from c-Abl inhibition," commented Milton Werner, Ph.D., President and Chief Executive Officer of Inhibikase. "As we look ahead, we expect to file our IND application for IkT-001Pro for the treatment of CML in the first quarter of 2022 as well as anticipate completing our Phase 1b study for Ikt-148009 in 2022."

Third Quarter Financial Results

Net Loss: Net loss for the quarter ended September 30, 2021, was $4.5 million, or $0.18 per share, compared to a net loss of $0.7 million, or $0.08 per share in the third quarter 2020.

R&D Expenses: Research and development expenses were $3.2 million for the quarter ended September 30, 2021 compared to $.1 million in the third quarter 2020. The increase was driven by a $0.3 million increase in grant related research expenditures and a $2.8 million increase in non-grant related research. The non-grant related research was expended primarily in connection with the Company’s Phase I Parkinson’s disease clinical trial.

SG&A Expenses: Selling, general and administrative expenses for the quarter ended September 30, 2021 were $1.6 million compared to $0.6 million for the third quarter in 2020. The increase was the result of increased non-cash stock compensation expense of $0.1 million, increased director and officer’s liability insurance of $0.4 million related to the Company’s IPO in December 2020, increased legal fees, board fees, investor relation and consulting fees of $0.3 million relating to operating as a public company registrant since December 2020 and a net increase of $0.2 million for other normal operating expenses.

Cash Position: Cash and cash equivalents were $45 million as of September 30, 2021.

On November 15, 2021 Vaccibody reported that (Press release, Vaccibody, NOV 15, 2021, View Source [SID1234595955])

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!

HIGHLIGHTS:
 Initiated the Phase 1b clinical trial in patients with locally advanced and metastatic tumors (VB N-02) in collaboration with Genentech (VB10.NEO individualized vaccine). First site opened in the USA
 Entered into worldwide license agreement with Adaptive Biotechnologies for clinically validated SARS-CoV-2 T cell epitopes Highlights after September 30, 2021:
 First subject dosed in a two-arm phase 1/2 clinical trial with a second generation and a third generation SARS-CoV-2 vaccine candidate  Reached a headcount of more than 100 people
 Continues to explore a potential listing of the company’s shares on Nasdaq and expects during 2022 to apply for a transfer of the listing of its shares to the main market of Oslo Stock Exchange R&D UPDATE Vaccibody’s modular technology platform is very versatile and may be adapted to generate the desired immune response profile. Hence, Vaccibody’s platform may be applied across a broad range of immunotherapy areas as innovative solutions to an unmet medical need. Vaccibody continues to increase the headcount across all functions including R&D to continue to build competencies and support the strategy execution. Please find below an update on Vaccibody’s current research and development activities.

Oncology VB10.16 VB10.16 is a therapeutic HPV vaccine directed against HPV16+ induced malignancies:
 Clinical trial VB C-02: o Clinical stage: Phase II o Indication: HPV16+ advanced, non-resectable cervical cancer o Up to 50 patients o ClinicalTrials.gov Identifier: NCT04405349 Vaccibody AS, Gaustadalléen 21, 0349 Oslo, Norway www.vaccibody.com Org.nr. 990 646 066 4 Status and highlights Investigational sites in 6 European countries are screening and enrolling patients. The trial is on track to complete enrolment during fourth quarter 2021. Vaccibody plans to report interim clinical data by the end of Q1 2022. The commercial potential in other HPV16 driven cancer indications such as HNSCC (Head and neck squamous cell carcinoma) is being explored. A development strategy update for VB10.16 will follow in 1H 2022

. VB10.NEO VB10.NEO is an individualized neoantigen cancer vaccine, exclusively licensed to Genentech:  Clinical trial VB N-01: o Clinical stage: Phase I/IIa o Cancer indications: Melanoma, non-small cell lung cancer (NSCLC), clear renal cell carcinoma, urothelial cancer or squamous cell carcinoma of the head and neck (SCCHN) o Fully enrolled o ClinicalTrials.gov Identifier: NCT03548467  Clinical trial VB N-02: o Clinical stage: Phase Ib o Cancer indications: Locally advanced and metastatic tumors o Up to 40 patients o ClinicalTrials.gov Identifier: NCT05018273 Status and highlights The first clinical site in the USA has been opened. The work on further site initiations in the USA and Europe continues. Infectious Diseases Vaccibody’s infectious disease initiatives spans both pre-clinical and clinical activities. VB10.COV2 Vaccibody has selected a 2-arm strategy for the VB10.COV2 project to fight SARS-CoV-2 variants of concern. VB10.2129 and VB10.2210 are two vaccine candidates designed based on Vaccibody’s modular and APC targeted technology:  In clinical trial VB-D-01, the two vaccine candidates, VB10.2129 and VB10.2210, are being investigated in previously vaccinated healthy volunteers. o VB10.2129-2nd generation vaccine addressing novel CoV-2 variants of concernVB10.2210-3rd generation universal broadly protective T cell vaccine, including T cell epitopes validated by Adaptive Biotechnologies

 Clinical stage: Phase 1/2
 Pathogen: SARS CoV-2  Up to 160 patients
 ClinicalTrials.gov Identifier: NCT05069623 Status and highlights Vaccibody reached the internal milestone of dosing the first subject with VB10.2129 in early November 2021.

With Vaccibody’s flexible and modular technology platform, it took only 267 days from design to first subject dosed. OTHER INFECTIOUS DISEASES Vaccibody has over the last years generated promising pre-clinical data in other infectious disease models. The Company has therefore initiated research discovery programs to explore and evaluate a focused set of pathogens as potential future clinical vaccine targets. Autoimmune disorders Autoimmune disorders are caused by unwanted immunogenicity to autoantigens.

Vaccibody continues to explore the modular technology platform and unique APC targeting approach to generate pre-clinical proof-of-concept for the ability to induce meaningful antigen-specific immune tolerance. The Company is investing significantly in the research area and is hiring to build further capacity and know-how. OTHER Capital market considerations Vaccibody continues to explore a potential listing of the company’s shares on the Nasdaq Global Market in the United States as first communicated in 1H 2021.

Furthermore, the Company expects during 2022 to apply for a transfer of the listing of its shares on the Oslo Stock Exchange from Euronext Growth Oslo to Oslo Børs, the main market of the Oslo Stock Exchange.

On November 15, 2021 Theseus Pharmaceuticals, Inc. (NASDAQ: THRX), a biopharmaceutical company focused on improving the lives of cancer patients through the discovery, development and commercialization of transformative targeted therapies, reported financial results for the third quarter ended September 30, 2021 (Press release, Theseus Pharmaceuticals, NOV 15, 2021, View Source [SID1234595624]).

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!

"At Theseus, we are leveraging our deep expertise in the development of targeted therapies to address the problem of drug resistance mutations in cancer," said Tim Clackson, Ph.D., President and Chief Executive Officer of Theseus Pharmaceuticals. "The third quarter marked two significant milestones for Theseus: our entrance into the public markets and the start of our transition into a clinical-stage company. The recent IND clearance for our lead candidate, THE-630, a pan-variant KIT inhibitor with the potential to address unmet need in patients with previously treated gastrointestinal stromal tumors (GIST), and the completion of our successful IPO position Theseus well to advance both the Phase 1/2 clinical trial of THE-630 and our pipeline of novel pan-variant inhibitors specifically designed to overcome the full range of drug resistance mutations."

Third Quarter Highlights and Upcoming Milestones:

Received FDA clearance of an investigational new drug (IND) application to evaluate THE-630 in patients with GIST. Theseus plans to initiate a Phase 1/2 dose escalation and expansion clinical trial of THE-630, its lead development program, in patients with previously treated advanced GIST between late fourth quarter 2021 and mid-first quarter 2022. THE-630 is a pan-variant inhibitor of the receptor tyrosine kinase KIT designed for patients with advanced GIST whose cancer has developed resistance to earlier lines of therapy.
Completed $178.8 million upsized initial public offering. In October 2021, Theseus sold 11,172,190 shares of common stock at a price to the pubic of $16.00 per share. The gross proceeds from the offering were approximately $178.8 million, before deducting underwriting discounts and commissions and other estimated offering expenses.
Leadership strengthened through appointments to senior scientific team. Theseus recently appointed Nachu Narasimhan, Ph.D., as Senior Vice President, Drug Metabolism and Preclinical Safety, and Len Rozamus as Senior Vice President, Technical Operations. Together, their deep experience in targeted oncology research and development will help to further advance Theseus’ pipeline.
Dr. Narasimhan brings over 30 years of experience in drug metabolism and bioanalytical disciplines and over 10 years’ experience in preclinical safety and clinical pharmacology. Dr. Narasimhan was most recently Vice President of Drug Metabolism and Clinical Pharmacology at Verastem Oncology. Previously, he contributed to the development and approval of several drugs while working at Merck, ARIAD Pharmaceuticals, and Bristol-Myers-Squibb.
Mr. Rozamus brings over 30 years of experience in pharmaceutical discovery and development, from pre-clinical programs through commercial products. Most recently, Mr. Rozamus served as Founder and President of Rozamus and Associates, Inc. Previously, his work while Senior Director of Manufacturing Operations at ARIAD Pharmaceuticals contributed to the approval of three oncology drugs.
Advanced fourth-generation epidermal growth factor receptor (EGFR) program towards development candidate nomination in the first half of 2022, and thereafter initiate IND-enabling studies. For its second development program, Theseus expects to nominate an EGFR candidate designed to inhibit the full range of single-, double-, and triple-mutant EGFR variants found in the tumors of patients with EGFR-mutant non-small cell lung cancer (NSCLC) that have developed resistance to osimertinib, including the C797S mutation.
One or more additional kinase targets expected to be nominated by the end of 2022.
Third Quarter Financial Results:

As of September 30, 2021, Theseus had cash and cash equivalents of $90.4 million, which does not include net proceeds from its IPO, which was completed in October 2021.
Theseus expects its cash and cash equivalents, including proceeds from the IPO, to fund operations and capital expenditures into the second half of 2024.
Research & Development expenses for the third quarter of 2021 were $5.0 million.
General & Administrative expenses for the third quarter of 2021 were $2.4 million.
Net Loss for the third quarter 2021 was $7.4 million, or $5.16 per share.